Conference Schedule
Monday, March 25th | Tuesday, March 26th | Wednesday, March 27th | Thursday, March 28th | |
---|---|---|---|---|
9.00-10.00 | Yeomans | Goldman | Schrefler | Sharon |
10.00-11.00 | Micheletti | Goriely | Arroyo | Giardina |
11.00-11.30 | Coffee Break | |||
11.30-12.30 | Howard | DeSimone | Deshpande | Netti |
12.30-14.30 | Lunch | |||
14.30-15.30 | Cerbino | Di Leonardo | Höhn | Del Alamo |
15.30-16.00 | Coffee Break | |||
16.00-17.00 | Maritan | Stocker | Fratzl | Laschi |
Contributions
Marino Arroyo The active mechanics of epithelial monolayers under stretch
Many biological processes in health and disease depend on the mechanics of epithelial tissues under stretch. However, the rheology of these active materials at different time-scales is poorly understood. A number of modelling frameworks have been proposed to understand the mechanics of cells and tissues. Ultimately, these mechanics depend on the integration of subcellular processes including cell volume regulation, or the dynamics of adhesion and cytoskeletal complexes. Despite much is known about these subcellular mechanisms, most modelling approaches for cells and tissues are phenomenological and miss this microscopic connection. Here, I will discuss a framework to generate out-of-equilibrium models and computations for the mechanics of cells and tissues starting from subcellular cytoskeletal dynamics, along with selected comparisons with experimental observations.
Roberto Cerbino The unjamming transition in dense cell collectives
Densely packed cells in a tissue are in a jammed, solid-like state that is characterised by little or no dynamics. Nevertheless, notable biological processes (e.g. wound healing, morphogenesis, cancer invasion) involve cellular rearrangements and collective migration. A gateway to this reacquired motility is the so-called unjamming transition: a solid-like tissue can locally "liquefy" with cells being able to move in small groups across the tissue, by still retaining an epithelial phenotype. In principle, unjamming may play a role in cancer dissemination and metastasis, as it does not require changes of identity and complex transcriptional rewiring programs typical of other migration modalities (e.g. the well-known epithelial to mesenchymal transition). However, the bio-molecular drive of unjamming, as well as its physiological and clinical relevance remain poorly understood. In this talk, I will describe recent results [1-4] obtained in experiments and simulations performed with dense 2D and 3D cell collectives (monolayers, cysts, spheroids and ex-vivo slices of breast ductal carcinoma in situ). In particular, I will focus on the recently discovered fact that elevation of the small GTPase RAB5A, a master regulator of endocytosis, causes dramatic behavioural changes in 2D and 3D collectives, with cells acquiring an emerging flocking-like coordinated motility that is typical of other organisms, such as birds or fish. Beyond briefly discussing the biochemical pathway that triggers cellular unjamming via flocking, I will detail the biophysical consequences of the resulting highly coordinated collective cell motility, in particular for cancer invasion and dissemination.
[1] C. Malinverno, S. Corallino et al, Nat. Mater. 16, 587–596 (2017)
[2] F. Giavazzi et al, J. Phys. D: Appl. Phys. 50, 384003 (2017)
[3] F. Giavazzi, M. Paoluzzi et al, Soft Matter 14, 3471-3477 (2018)
[4] A. Palamidessi et al, bioRxiv 388553; doi: http://dx.doi.org/10.1101/388553.
[5] F. Giavazzi et al., Frontiers in Physics 6 120 (2018)
Juan Del Alamo Experimental studies of soft adhesive locomotion. From Leukocytes to creepy crawlies.
The locomotion of soft-bodied organisms, from amoeboid cells with lipid membranes to multicellular organisms lacking rigid skeletal support, has applications in diverse fields such as ecology, medicine and bio-inspired engineering design. By combining microfabrication and traction force microscopy, we developed various in vitro assays to study the mechanics of locomotion of soft-bodied organisms in a wide range of length scales (10 μm – 10 cm). Despite major differences in their biology, the locomotion of soft-bodied organisms follows similar mechanical principles: they apply periodic waves of traction stresses on their substrate.
We will present data suggesting that in small-scale organisms like amoeboid cells, standing waves of traction stresses allow for overcoming the stabilizing effect of the surface tension created by the cell envelope. In larger organisms like worms and gastropods, traveling waves of shear traction stress provide robust propulsive forces in the presence of heterogeneous resistance from the environment.
We will pay particular attention to the blood parasite Schistosoma mansoni, a flatworm that exhibits remarkable locomotor versatility under different environmental conditions. We will show that in unconfined settings, the parasite undergoes two-anchor marching mediated by its oral and ventral suckers, whose adhesion strength is adjusted to withstand hemodynamic forces. Under confinement, the worm switches to retrograde peristaltic waves. We will argue that, while this gait requires tight coordination between muscle contraction and substrate friction, it allows the worm to reverse its direction of locomotion without turning its body, which is likely advantageous to maneuver in the narrow-bore veins the parasite dwells.
Vikram Deshpande Entropic forces drive cellular contact guidance
Contact guidance--the widely-known phenomenon of cell alignment induced by anisotropic environmental features--is an essential step in the organization of adherent cells, but the mechanisms by which cells achieve this orientational ordering remain unclear. Myofibroblasts seeded on substrates micropatterned with stripes of fibronectin show that contact guidance emerges at stripe widths much greater than the cell size. To understand the origins of this surprising observation, we combined morphometric analysis of cells and their subcellular components with a novel statistical framework for modelling non-thermal fluctuations of living cells [1,2]. This modelling framework is shown to predict not only the trends but also the statistical variability of a wide range of biological observables including cell (and nucleus) shapes, sizes and orientations, as well as stress-fibre arrangements within the cells with remarkable fidelity with a single set of cell parameters. By comparing observations and theory, we identified two regimes of contact guidance: (i) guidance on stripe widths smaller than the cell size (𝑤 ≤ 160 μm), which is accompanied by biochemical changes within the cells, including increasing stress-fibre polarisation and cell elongation, and (ii) entropic guidance on larger stripe widths, which is governed by fluctuations in the cell morphology. Overall, our findings suggest an entropy-mediated mechanism for contact guidance associated with the tendency of cells to maximise their morphological entropy through shape fluctuations.
[1] Shishvan, S. S., A. Vigliotti, and V. S. Deshpande. (2018) The homeostatic ensemble for cells. Biomech Model Mechanobiol. https://doi.org/10.1007/s10237-018-1048-1
[2] A.B.C. Buskermolen, H. Suresh, S.S. Shishvan, A. Vigliotti, A. DeSimone, N.A. Kurniawan, C.V.C. Bouten and V.S. Deshpande. Entropic forces drive cellular contact guidance, submitted, 2019
Antonio DeSimone Micromotility by shape control
Locomotion strategies employed by unicellular organism are a rich source of inspiration for studying mechanisms for shape control. In fact, in an overwhelming majority of cases, biological locomotion can be described as the result of the body pushing against the world, by using shape change. Motion is then a result Newton’s third and second law: the world reacts with a force that can be exploited by the body as a propulsive force, which puts the body into motion following the laws of mechanics. Strategies employed by unicellular organisms are particularly interesting because they are invisible to the naked eye, and offer surprising new solutions to the question of how shape can be controlled.
In recent years, we have studied locomotion and shape control in Euglena gracilis using a broad range of tools ranging from theoretical and computational mechanics, to experiment and observations at the microscope, to manufacturing of prototypes. This unicellular protist is particularly intriguing because it can adopt different motility strategies: swimming by flagellar propulsion, or crawling thanks to large amplitude shape changes of the whole body (a behavior known as metaboly). We will survey our most recent findings within this stream of research.
[1] Rossi, M., Cicconofri, G., Beran, A., Noselli, G., DeSimone, A.: Kinematics of flagellar swimming in Euglena gracilis: Helical trajectories and flagellar shapes. PNAS 2017
[2] Cicconofri, G., DeSimone, A.: Modeling biological and bio-inspired swimming at microscopic scales: recent results and perspectives. Computer and Fluids 2019
[3] Noselli, G., Beran, A., Arroyo, M., DeSimone, A.: Swimming Euglena respond to confinement with a behavioral change enabling effective crawling. Nature Physics 2019
[4] Noselli, G. Arroyo, M., DeSimone, A.: Smart helical structured inspired by the pellicle of euglenoids. J Mech Phys Solids 2019
Roberto Di Leonardo Using light to understand and control active matter
Dense suspensions of swimming bacteria display striking motions that appear extremely vivid when compared to the thermal agitation of colloidal particles of comparable size. These suspensions belong to a broader class of non-equilibrium systems that are now collectively referred to as active matter. Fundamental research in the physics of active matter investigates the basic principles governing non equilibrium phenomena such as self-propulsion, collective behavior and rectification. From a more engineering point of view, however, active particles could potentially provide the active "atoms" of a new class of smart materials with unique response characteristics. Using advanced 3D optical imaging, micromanipulation and microfabrication tools, we study complex phenomena in active matter using direct and quantitative methods. I will review our recent work in this direction, from the fluid and statistical mechanics of bacterial movements in structured environments to the use of genetically modified bacteria as propellers for micromachines or as a "living" paint that can be controlled by light.
Peter Fratzl Motility through water absorption in plant materials
Diverse plants synthesize materials that actuate with varying humidity and provide motility in the context of seed dispersal. These (non-living) shape-changing materials are composites based on cellulose nanofibrils in a polysaccharide-rich matrix that swells with water uptake. This combination of a swelling matrix and inextensible fibrils provides actuation depending on fiber architecture [1]. The energy source for the movement is the interaction of water from the atmosphere with cellulose and other polysaccharides in the cell wall [2]. Such structures can be rationalized through numerical modelling and concepts for actuation systems may be derived from them [3]. A special case are seed pods from Banksia trees, in which fire triggers the opening of the woody fruits, followed by humidity-mediated seed release after the passage of fire [4]. In summary, plant seed pods are interesting models for a wide range of small robotic devices that fulfill simple predefined functions in remote locations.
[1] I. Burgert and P. Fratzl, Phil. Trans. R. Soc. A 2009, 367: 1541–57; R. Elbaum et al. Science 2007, 316: 884-6; P. Fratzl and F. G. Barth, Nature 2009, 462, 442–8.
[2] L. Bertinetti, F. D. Fischer and P. Fratzl, Phys. Rev. Lett. 2013, 111:238001; L. Bertinetti, P. Fratzl, T. Zemb, New J. Phys. 2016, 18:083048; A. Barbetta, P. Fratzl, T. Zemb, L. Bertinetti, Adv. Mater. Interfaces 2017, 4:1600437.
[3] L. Guiducci et al., J. R. Soc. Interface 2014, 11, 20140458; Adv. Mater. Interfaces 2015, 2, 1500011; PLoS One 2016, 11, e0163506.
[4] J. C. Huss, et al., Adv. Sci. 2018, 5, 1700572; J. C. Huss, et al., J. Roy. Soc. Interface 2018, 15, 20180190.
Irene Giardina Behavioral inertia, scaling and collective behaviour in animal groups
Many animal aggregations display collective patterns on the large scale, ultimately due to the interactions between the individuals in the group. Recent findings on flocks of birds and swarms of insects show that these groups exhibit strong mutual correlations and quick mechanisms of information propagation, signatures of the efficient collective response to external perturbations. Besides, they obey static and dynamic scaling laws suggesting that we can use a statistical physics approach to describe the large scale, and define novel "classes" of behaviour. In this talk I will review recent experiments on flocks and swarms and discuss how a crucial ingredient, behavioural inertia, is necessary to theoretically explain the scaling behaviour and the dispersion law observed in the data.
Daniel Goldman Macroscopic mimics of microscopic mobility
Microorganisms encounter environments containing complex mixtures of soft materials displaying fluid and solid-like properties. It is typically assumed that a key difference between self-propulsion in the microworld and in the world inhabited by macroscopic organisms (like those studied in my lab) is that inertial effects are negligible in the former, but not the latter. However, our experimental studies and predictive theoretical models of organisms like lizards and snakes moving in granular media have revealed that locomotion (e.g. sand-swimming) in these frictionally dissipative environments bears similarities to microscopic locomotors. As such, we are able to use tools (like Resistive Force Theory, geometric mechanics) to gain insight into optimal patterns of self-propulsion and construct relatively simple physical robot models to test biological hypotheses. Inspired by these discoveries, the increasing ease of creating robophysical models at the macroscale, and the ability to conveniently control rheological properties of dry granular media (using systems like air-fluidized beds), we posit that insights from successful granular locomotion (including dealing with environmental heterogeneities, fluctuations and local sensing) can be of use in design and control of mobile systems on much smaller scales.
[1] Physics approaches to natural locomotion: Every robot is an experiment, Yasemin Ozkan Aydin, Jennifer M. Rieser, Christian M. Hubicki, William Savoie, Daniel I. Goldman, Chapter 6: Robotic Systems and Autonomous Platforms, 1st Edition, Advances in Materials and Manufacturing (2018) PDF
[2] A review on locomotion robophysics: the study of movement at the intersection of robotics, soft matter, and dynamical systems, Jeffrey Aguilar,Tingnan Zhang, Feifei Qian, Mark Kingsbury, Benjamin McInroe, Nicole Mazouchova, Chen Li, Ryan Maladen, Chaohui Gong, Matt Travers, Ross L. Hatton, Howie Choset, Paul B. Umbanhowar, and Daniel I. Goldman, Reports on Progress in Physics 79 110001 (2016) PDF
[3] Beneath our feet: strategies for locomotion in granular media, A.E. Hosoi and Daniel I. Goldman, Annual Review of Fluid Mechanics, 47, 431-453 (2015) PDF
[4] The effectiveness of resistive force theory in granular locomotion, Tingnan Zhang and Daniel I. Goldman, Physics of Fluids, 26, 101308 (2014) PDF
[5] Swimming in the desert, Yang Ding, Chen Li, and Daniel I. Goldman, Physics Today, November, pg. 68 (2013) PDF
Alain Goriely Filament motion through growth: principles and applications
For many biological systems, motion is limited or driven by growth. This is true for most plant motions as well as for the motion of axons in the early development of the brain. What are the guiding principles of motion through growth? It usually combines the relative motion of part of the body by addition of mass (apical or otherwise) for linear elongation controlled by active forces and the clever use of material anisotropy for the creation of curvature and torsion. In this talk, I will review these basic principles and see how they apply to different biological settings.
Stephanie Hoehn Morphogenesis is stressful - Mechanics of cell sheet folding in volvocalean algae
Living tissues are intelligent materials that can change their mechanical properties while they develop. In spite of extensive studies in multiple model organisms we are only just beginning to understand these dynamic properties and their role in tissue development. Although many tissues are known to exhibit visco-elastic properties, it is unclear which properties dominate three-dimensional shape changes of cellular monolayers, such as epithelia.
The embryonic inversion process in the micro-algal family Volvocales is uniquely suited for comparative studies on epithelial morphogenesis. Volvocalean embryos consist of cup-shaped or spherical cellular monolayers which invert their curvature in order to expose their flagella. These inversion processes involve a range of species-dependant complexity in terms of both the local cell shape changes and the resulting deformations of the cell sheet. Volvox globator exhibits one of the most striking processes of cell sheet folding: Through inwards folding along the equator the initially spherical cell sheet adopts a mushroom shape and eventually turns itself entirely inside-out [1]. A combination of light sheet microscopy and mathematical modelling revealed that the equatorial bending is complemented by active contraction in the posterior and expansion in the anterior hemisphere [2,3]. Laser ablation experiments are used to determine the role that the cell sheet’s elastic properties play in these deformations.
[1] Höhn S and Hallmann A. BMC Biology 9, 89 (2011)
[2] Höhn S, Honerkamp-Smith AR, Haas PA, Khuc Trong P, and Goldstein RE. Physical Review Letters 114, 178101 (2015)
[3] Haas PA, Höhn S, Honerkamp-Smith AR, Kirkegaard JB, and Goldstein RE. PLOS Biology 16, e2005536 (2018)
Jonathon Howard Curvature feedback coordinates axonemal dyneins to drive the flagellar beat in Chamydomonas
The snake-like beating patterns of sperm tails and the breast-stroke-like swimming strokes of ciliated organisms are driven by the molecular motor dynein. This motor protein generates sliding forces between adjacent microtubule doublets within the axoneme, the motile cytoskeletal structure within cilia and flagella. To create regular, oscillatory beating patterns, the activities of the dyneins must be coordinated, both spatially and temporally. It is thought that coordination is mediated by stresses or strains that build up within the moving axoneme, but it is not known which components of stress or strain are involved, nor how they feed back on the dyneins. To answer this question, we have measured the beating patterns of isolated, reactivate axonemes of the unicellular alga Chlamydomonas reinhardtii [1]. We compared the measurements in wild-type and mutant cells with models derived from different feedback mechanisms. We found that regulation by changes in axonemal curvature was the only mechanism that accords with the measurements [2]. We suggest that distortions due to bending of twisted axonemes may provide a mechanism by which the motors sense curvature [3]. To facilitate modeling studies of axonemal beats, we have published a simplified version of our model [4].
[1] Geyer, V. F., Sartori, P., Friedrich, B. M., Jülicher, F., & Howard, J. Current Biology 26, 1098–1103 (2016)
[2] Sartori, P., Geyer, V. F., Scholich, A., Jülicher, F., & Howard, J. eLife, 5, 343 doi.org/10.7554/eLife.13258 (2016)
[3] Sartori, P., Geyer, V. F., Howard, J., & Jülicher, F. Physical Review E, 94.042426 (2016)
[4] Geyer, V. F., Sartori, P., Jülicher, F., & Howard, J. In Dyneins (1st ed., Vol. 32, pp. 192–212). Academic Press. (2017)
Cecilia Laschi Lessons from nature and soft robotics: what an octopus can teach to roboticists
Largely inspired by the observation of the role of soft tissues in living organisms [1], the use of soft materials for building robots is recognized as one of the current challenges for pushing the boundaries of robotics technologies [2] and building robots for service tasks in natural environments. The study of living organisms sheds light on principles that can be fruitfully adopted to develop further robot abilities [3], as they exploit soft tissues and compliant structures to move effectively in complex natural environments [4]. The octopus is an excellent model for this [5] and provides principles for locomotion [6], swimming, and manipulation. While in robotics soft bodies pose important challenges for modelling and for controlling their behavior, at the same time living organisms like the octopus provide principles that can help soft robot control [7].
[1] S. Kim, C. Laschi, B. Trimmer, “Soft robotics: a bioinspired evolution in robotics”, Trends in Biotechnology, No.31, 2013, pp.287-294.
[2] C. Laschi, M. Cianchetti, “Soft Robotics: New Perspectives for Robot Bodyware and Control”, Frontiers in Bioengineering and Biotechnology, No.2, 2014
[3] C. Laschi, M. Cianchetti, B. Mazzolai, “Soft robotics: Technologies and systems pushing the boundaries of robot abilities”, Science Robotics 1(1), 2016.
[4] C. Laschi; B. Mazzolai, "Lessons from Animals and Plants: The Symbiosis of Morphological Computation and Soft Robotics", IEEE Robotics and Automation Magazine 23(3), 2016.
[5] C. Laschi, “Robot Octopus Points the Way to Soft Robotics With Eight Wiggly Arms”, IEEE Spectrum 1, 2016.
[6] M. Calisti, G. Picardi, C. Laschi, “Fundamentals of soft robot locomotion”, Journal of The Royal Society Interface 14(130), 2017
[7] T. George Thuruthel, Y. Ansari, E. Falotico, C. Laschi, “Control Strategies for Soft Robotic Manipulators: A Survey”, Soft Robotics 5(2), 2018, pp.149-163.
Amos Maritan Optimality and scaling in living systems and ecological communities
Forests are terrestrial ecosystems with a high degree of structural and functional diversity: in the tropics, there often are hundreds of coexisting plant species with different habitats and thousands of consumers, each of them with interspecific relationships with plant species. This leads to a multitude of interconnected food webs and complex fluxes of matter and energy. We demonstrate an astounding simplicity underlying the apparent bewildering complexity of forests. Our starting point is based on an optimization principle for understanding and making predictions that are in accord with empirical data. The simplicity originates from the well-known empirical observation that power law relationships, also known as allometric scaling, are pervasive in tree communities and, more in general, in complex ecological communities.
Cristian Micheletti Knotted DNA: conformational, dynamical and pore-translocation properties
Knots and supercoiling are both introduced in bacterial plasmids by catalytic processes involving DNA strand passages. I will report on a recent study where we used molecular dynamics simulations and a mesoscopic DNA model, to study the simultaneous presence of knots and supercoiling in DNA rings and the kinetic and metric implications which may be relevant for the simplifying action of topoisomerases [1]. Finally, I will discuss how the same modelling and simulation approach [2] can be used shed light on the complex experimental phenomenology of knotted DNA translocating through solid state nanopores [3].
[1] L. Coronel, A. Suma and C. Micheletti Dynamics of supercoiled DNA with complex knots Nucleic Acids Res., 2018, 46 , 7533 .
[2] A. Suma and C. Micheletti Pore translocation of knotted DNA rings Proc. Natl. Acad. Sci. USA, 2017, 114 , E2991-E2997.
[3] Plesa C, et al. Direct observation of DNA knots using a solid-state nanopore. Nat Nanotechnol (2016) 11:1093–1097.
Paolo Netti Cell instructive materials to control and guide cell locomotion
Cell migration is a crucial aspect of diverse biological events including morphogenesis, tissue repair and homeostasis [1]. Specifically engineered culturing platform demonstrated that several biochemical and biophysical signals strongly affect cell migration [2]. In particular, patterns of topographic, mechanical or biomolecular signals proved to exert a strong control over cell adhesion and cell generated forces that fundamentally govern motility, both at a single cell or collective level [3]. In this presentation, strategies aimed at encoding signals constituting sets of instructions that regulate cell adhesion, cell mechanics and migration will be illustrated. Particular emphasis will be given on the interface between cells and material, the locus in which cells recognize and respond to adhesion signals and patterns thereof. Signals presented at different length scales (nano-, submicron- and micron-scale) target different cell compartments and can differently affect cell adhesion, orientation and migration [4,5]. Finally, examples on how cell generated forces and motility may be exploited to sculpt tissue shape and microarchitecture will be presented and discussed [6].
This talk aims at highlighting the central role of material signals, which – if sapiently organized – may dictate cell fate and functions through the surface-adhesion-cytoskeleton axis.
[1] Trepat X, Chen Z, Jacobson K. Cell migration. Compr Physiol. 2, 2369-92, 2012.
[2] Ventre M, Causa F, Netti PA. Determinants of cell-material crosstalk at the interface: towards engineering of cell instructive materials. J R Soc Interface. 9, 2017-32, 2012
[3] Ventre M, Netti PA. Engineering Cell Instructive Materials To Control Cell Fate and Functions through Material Cues and Surface Patterning. ACS Appl Mater Interfaces. 8, 14896-908, 2016
[4] Ventre M, Natale CF, Rianna C, Netti PA. Topographic cell instructive patterns to control cell adhesion, polarization and migration. J R Soc Interface. 11, 20140687, 2014.
[5] Natale CF, Ventre M, Netti PA. Tuning the material-cytoskeleton crosstalk via nanoconfinement of focal adhesions. Biomaterials 35, 2743-51, 2014.
[6] Iannone M, Ventre M, Formisano L, Casalino L, Patriarca EJ, Netti PA. Nanoengineered surfaces for focal adhesion guidance trigger mesenchymal stem cell self-organization and tenogenesis. Nano Lett. 15, 1517-25, 201
Bernhard Schrefler Modeling drug delivery and efficiency in the tumor microenvironment
Computational Transport Oncophysics [1] provides the computational tools which, together with imaging, analysis and quantification, will contribute to rationalize the delivery of therapeutic agents and to evaluate their efficiency, forming an oncophysical modeling framework. This framework should comprise a tumor growth model within the local tumor environment, coupled with a patient specific biodistribution model. For the first one we present a very general multiphase flow model in an extracellular matrix (ECM), dealt with as a deforming porous solid which may undergo remodeling; it comprises three fluid phases, i.e. tumor cells (TCs), divided into living and necrotic cells, healthy cells (HCs) and interstitial fluid (IF). The IF transports chemical species such as tumor angiogenic factor (TAF), nutrients and therapeutic agents. Transport of these species within extravascular space takes place by convection and diffusion. Coopted blood vessels are included as line elements with blood flow exchanging nutrients and therapeutic agents with the IF. Angiogenesis is represented by the blood vessel density (density of newly created endothelial cells). The model accounts not only for growth and necrosis but also for migration of cells through the ECM, for different stiffness of the cell population with respect to the ECM, build-up of cortical tension between healthy and tumor tissues and possible invasion of the tumor tissue by the healthy tissue or vice versa, mediated by these cortical tensions. Further it allows for modeling lysis, adhesion of the cells to their ECMs, adhesion among cells and possible detachment as well as the effects of drugs. For a fast evaluation of the drug effects also a simpler bi-phasic model with cells and ECM lumped together, but permeated by an IF, may be used; it excludes however several of the above mentioned features. Examples for both models will be shown.
[1] Michor, F., J. Liphardt, M. Ferrari, and J. Widom, What does physics have to do with cancer? Nature Reviews Cancer, 2011. 11(9): p. 657-670.
Eran Sharon Propagating chemical waves as an engine for autonomous flapping sheets
Autonomous actuation of soft tissues is common in a wide variety of natural systems, both on cellular and macroscopic scales. The success in mimicking such systems in manmade structures is limited. We present an autonomous shape-transforming sheet and suggest a framework for its quantitative analysis and design.
Thin sheets made of NIPA- Ruthenium copolymer gel are placed in a solution of the Belousov-Zhabotinsky (BZ) reactants, leading to the spontaneous periodic propagation of chemical fronts within the gel. These front lead to local contraction and expansion of the gel, driving its periodic buckling into 3D evolving shapes. Using the theory of incompatible elastic sheets, we describe the system as an evolving non-Euclidean plate. The reference metric of the plate varies in time and space according to the BZ field evolution. We obtain a connection between the BZ field and the 3D configurations and confirm it experimentally.
Roman Stocker Microbial motility in the ocean
Although we now know that microorganisms rule the oceans - controlling productivity and biogeochemical cycles - we largely ignore how they are affected by typical fluid flow conditions. For example, microbes are routinely exposed to turbulence, yet physicists have ignored microbes and biologists have ignored turbulence. Here I present microfluidic and millifluidic experiments, combined with mathematical models, to show that fluid flow can have profound effects on the biomechanics and the ecology of swimming microorganisms. I illustrate this through a series of examples, and will focus in particular on 'gravitaxis', the tendency of many phytoplankton species to swim along the direction of gravity. I will show that, in the presence of flow, gravitaxis results in intense clustering of cells in layers and patches, akin to those often observed by oceanographers, which can have profound effects on plankton population dynamics. Intriguingly, plankton seem to 'know fluid mechanics' and I will present recent evidence that they are able to actively evade turbulence by sensing the simplest among the cues inherent in small-scale turbulent eddies. In addition to representing a new class of active particle problems that promises to keep the fluid mechanician busy for some time to come, these processes are environmentally important because they affect the ecological dynamics and biogeochemical consequences of some of the most important players in aquatic ecosystems.
Julia Yeomans Self-propelled topological defects in active matter
Active materials, such as bacteria, molecular motors and self-propelled colloids, are Nature’s engines. They continuously transform chemical energy from their environment to mechanical work. Dense active matter shows mesoscale turbulence, the emergence of chaotic flow structures characterised by high vorticity and self-propelled topological defects.
The chaotic nature of active turbulence means that it is likely to be difficult to harness its energy. Hence it is interesting to consider ways to `tame' active turbulence, channeling the energy input into coherent flows. This can be done by screening hydrodynamics through confinement or friction, and I will describe flow patterns and defect trajectories in active matter in confined geometries.
Moreover the ideas of active matter suggest new ways of interpreting cell motility and cell division. In particular recent results indicate that active topological defects may help to regulate turnover in epithelial cell layers and contribute to controlling the structure of bacterial colonies.
Many biological processes in health and disease depend on the mechanics of epithelial tissues under stretch. However, the rheology of these active materials at different time-scales is poorly understood. A number of modelling frameworks have been proposed to understand the mechanics of cells and tissues. Ultimately, these mechanics depend on the integration of subcellular processes including cell volume regulation, or the dynamics of adhesion and cytoskeletal complexes. Despite much is known about these subcellular mechanisms, most modelling approaches for cells and tissues are phenomenological and miss this microscopic connection. Here, I will discuss a framework to generate out-of-equilibrium models and computations for the mechanics of cells and tissues starting from subcellular cytoskeletal dynamics, along with selected comparisons with experimental observations.
Roberto Cerbino The unjamming transition in dense cell collectives
Densely packed cells in a tissue are in a jammed, solid-like state that is characterised by little or no dynamics. Nevertheless, notable biological processes (e.g. wound healing, morphogenesis, cancer invasion) involve cellular rearrangements and collective migration. A gateway to this reacquired motility is the so-called unjamming transition: a solid-like tissue can locally "liquefy" with cells being able to move in small groups across the tissue, by still retaining an epithelial phenotype. In principle, unjamming may play a role in cancer dissemination and metastasis, as it does not require changes of identity and complex transcriptional rewiring programs typical of other migration modalities (e.g. the well-known epithelial to mesenchymal transition). However, the bio-molecular drive of unjamming, as well as its physiological and clinical relevance remain poorly understood. In this talk, I will describe recent results [1-4] obtained in experiments and simulations performed with dense 2D and 3D cell collectives (monolayers, cysts, spheroids and ex-vivo slices of breast ductal carcinoma in situ). In particular, I will focus on the recently discovered fact that elevation of the small GTPase RAB5A, a master regulator of endocytosis, causes dramatic behavioural changes in 2D and 3D collectives, with cells acquiring an emerging flocking-like coordinated motility that is typical of other organisms, such as birds or fish. Beyond briefly discussing the biochemical pathway that triggers cellular unjamming via flocking, I will detail the biophysical consequences of the resulting highly coordinated collective cell motility, in particular for cancer invasion and dissemination.
[1] C. Malinverno, S. Corallino et al, Nat. Mater. 16, 587–596 (2017)
[2] F. Giavazzi et al, J. Phys. D: Appl. Phys. 50, 384003 (2017)
[3] F. Giavazzi, M. Paoluzzi et al, Soft Matter 14, 3471-3477 (2018)
[4] A. Palamidessi et al, bioRxiv 388553; doi: http://dx.doi.org/10.1101/388553.
[5] F. Giavazzi et al., Frontiers in Physics 6 120 (2018)
Juan Del Alamo Experimental studies of soft adhesive locomotion. From Leukocytes to creepy crawlies.
The locomotion of soft-bodied organisms, from amoeboid cells with lipid membranes to multicellular organisms lacking rigid skeletal support, has applications in diverse fields such as ecology, medicine and bio-inspired engineering design. By combining microfabrication and traction force microscopy, we developed various in vitro assays to study the mechanics of locomotion of soft-bodied organisms in a wide range of length scales (10 μm – 10 cm). Despite major differences in their biology, the locomotion of soft-bodied organisms follows similar mechanical principles: they apply periodic waves of traction stresses on their substrate.
We will present data suggesting that in small-scale organisms like amoeboid cells, standing waves of traction stresses allow for overcoming the stabilizing effect of the surface tension created by the cell envelope. In larger organisms like worms and gastropods, traveling waves of shear traction stress provide robust propulsive forces in the presence of heterogeneous resistance from the environment.
We will pay particular attention to the blood parasite Schistosoma mansoni, a flatworm that exhibits remarkable locomotor versatility under different environmental conditions. We will show that in unconfined settings, the parasite undergoes two-anchor marching mediated by its oral and ventral suckers, whose adhesion strength is adjusted to withstand hemodynamic forces. Under confinement, the worm switches to retrograde peristaltic waves. We will argue that, while this gait requires tight coordination between muscle contraction and substrate friction, it allows the worm to reverse its direction of locomotion without turning its body, which is likely advantageous to maneuver in the narrow-bore veins the parasite dwells.
Vikram Deshpande Entropic forces drive cellular contact guidance
Contact guidance--the widely-known phenomenon of cell alignment induced by anisotropic environmental features--is an essential step in the organization of adherent cells, but the mechanisms by which cells achieve this orientational ordering remain unclear. Myofibroblasts seeded on substrates micropatterned with stripes of fibronectin show that contact guidance emerges at stripe widths much greater than the cell size. To understand the origins of this surprising observation, we combined morphometric analysis of cells and their subcellular components with a novel statistical framework for modelling non-thermal fluctuations of living cells [1,2]. This modelling framework is shown to predict not only the trends but also the statistical variability of a wide range of biological observables including cell (and nucleus) shapes, sizes and orientations, as well as stress-fibre arrangements within the cells with remarkable fidelity with a single set of cell parameters. By comparing observations and theory, we identified two regimes of contact guidance: (i) guidance on stripe widths smaller than the cell size (𝑤 ≤ 160 μm), which is accompanied by biochemical changes within the cells, including increasing stress-fibre polarisation and cell elongation, and (ii) entropic guidance on larger stripe widths, which is governed by fluctuations in the cell morphology. Overall, our findings suggest an entropy-mediated mechanism for contact guidance associated with the tendency of cells to maximise their morphological entropy through shape fluctuations.
[1] Shishvan, S. S., A. Vigliotti, and V. S. Deshpande. (2018) The homeostatic ensemble for cells. Biomech Model Mechanobiol. https://doi.org/10.1007/s10237-018-1048-1
[2] A.B.C. Buskermolen, H. Suresh, S.S. Shishvan, A. Vigliotti, A. DeSimone, N.A. Kurniawan, C.V.C. Bouten and V.S. Deshpande. Entropic forces drive cellular contact guidance, submitted, 2019
Antonio DeSimone Micromotility by shape control
Locomotion strategies employed by unicellular organism are a rich source of inspiration for studying mechanisms for shape control. In fact, in an overwhelming majority of cases, biological locomotion can be described as the result of the body pushing against the world, by using shape change. Motion is then a result Newton’s third and second law: the world reacts with a force that can be exploited by the body as a propulsive force, which puts the body into motion following the laws of mechanics. Strategies employed by unicellular organisms are particularly interesting because they are invisible to the naked eye, and offer surprising new solutions to the question of how shape can be controlled.
In recent years, we have studied locomotion and shape control in Euglena gracilis using a broad range of tools ranging from theoretical and computational mechanics, to experiment and observations at the microscope, to manufacturing of prototypes. This unicellular protist is particularly intriguing because it can adopt different motility strategies: swimming by flagellar propulsion, or crawling thanks to large amplitude shape changes of the whole body (a behavior known as metaboly). We will survey our most recent findings within this stream of research.
[1] Rossi, M., Cicconofri, G., Beran, A., Noselli, G., DeSimone, A.: Kinematics of flagellar swimming in Euglena gracilis: Helical trajectories and flagellar shapes. PNAS 2017
[2] Cicconofri, G., DeSimone, A.: Modeling biological and bio-inspired swimming at microscopic scales: recent results and perspectives. Computer and Fluids 2019
[3] Noselli, G., Beran, A., Arroyo, M., DeSimone, A.: Swimming Euglena respond to confinement with a behavioral change enabling effective crawling. Nature Physics 2019
[4] Noselli, G. Arroyo, M., DeSimone, A.: Smart helical structured inspired by the pellicle of euglenoids. J Mech Phys Solids 2019
Roberto Di Leonardo Using light to understand and control active matter
Dense suspensions of swimming bacteria display striking motions that appear extremely vivid when compared to the thermal agitation of colloidal particles of comparable size. These suspensions belong to a broader class of non-equilibrium systems that are now collectively referred to as active matter. Fundamental research in the physics of active matter investigates the basic principles governing non equilibrium phenomena such as self-propulsion, collective behavior and rectification. From a more engineering point of view, however, active particles could potentially provide the active "atoms" of a new class of smart materials with unique response characteristics. Using advanced 3D optical imaging, micromanipulation and microfabrication tools, we study complex phenomena in active matter using direct and quantitative methods. I will review our recent work in this direction, from the fluid and statistical mechanics of bacterial movements in structured environments to the use of genetically modified bacteria as propellers for micromachines or as a "living" paint that can be controlled by light.
Peter Fratzl Motility through water absorption in plant materials
Diverse plants synthesize materials that actuate with varying humidity and provide motility in the context of seed dispersal. These (non-living) shape-changing materials are composites based on cellulose nanofibrils in a polysaccharide-rich matrix that swells with water uptake. This combination of a swelling matrix and inextensible fibrils provides actuation depending on fiber architecture [1]. The energy source for the movement is the interaction of water from the atmosphere with cellulose and other polysaccharides in the cell wall [2]. Such structures can be rationalized through numerical modelling and concepts for actuation systems may be derived from them [3]. A special case are seed pods from Banksia trees, in which fire triggers the opening of the woody fruits, followed by humidity-mediated seed release after the passage of fire [4]. In summary, plant seed pods are interesting models for a wide range of small robotic devices that fulfill simple predefined functions in remote locations.
[1] I. Burgert and P. Fratzl, Phil. Trans. R. Soc. A 2009, 367: 1541–57; R. Elbaum et al. Science 2007, 316: 884-6; P. Fratzl and F. G. Barth, Nature 2009, 462, 442–8.
[2] L. Bertinetti, F. D. Fischer and P. Fratzl, Phys. Rev. Lett. 2013, 111:238001; L. Bertinetti, P. Fratzl, T. Zemb, New J. Phys. 2016, 18:083048; A. Barbetta, P. Fratzl, T. Zemb, L. Bertinetti, Adv. Mater. Interfaces 2017, 4:1600437.
[3] L. Guiducci et al., J. R. Soc. Interface 2014, 11, 20140458; Adv. Mater. Interfaces 2015, 2, 1500011; PLoS One 2016, 11, e0163506.
[4] J. C. Huss, et al., Adv. Sci. 2018, 5, 1700572; J. C. Huss, et al., J. Roy. Soc. Interface 2018, 15, 20180190.
Irene Giardina Behavioral inertia, scaling and collective behaviour in animal groups
Many animal aggregations display collective patterns on the large scale, ultimately due to the interactions between the individuals in the group. Recent findings on flocks of birds and swarms of insects show that these groups exhibit strong mutual correlations and quick mechanisms of information propagation, signatures of the efficient collective response to external perturbations. Besides, they obey static and dynamic scaling laws suggesting that we can use a statistical physics approach to describe the large scale, and define novel "classes" of behaviour. In this talk I will review recent experiments on flocks and swarms and discuss how a crucial ingredient, behavioural inertia, is necessary to theoretically explain the scaling behaviour and the dispersion law observed in the data.
Daniel Goldman Macroscopic mimics of microscopic mobility
Microorganisms encounter environments containing complex mixtures of soft materials displaying fluid and solid-like properties. It is typically assumed that a key difference between self-propulsion in the microworld and in the world inhabited by macroscopic organisms (like those studied in my lab) is that inertial effects are negligible in the former, but not the latter. However, our experimental studies and predictive theoretical models of organisms like lizards and snakes moving in granular media have revealed that locomotion (e.g. sand-swimming) in these frictionally dissipative environments bears similarities to microscopic locomotors. As such, we are able to use tools (like Resistive Force Theory, geometric mechanics) to gain insight into optimal patterns of self-propulsion and construct relatively simple physical robot models to test biological hypotheses. Inspired by these discoveries, the increasing ease of creating robophysical models at the macroscale, and the ability to conveniently control rheological properties of dry granular media (using systems like air-fluidized beds), we posit that insights from successful granular locomotion (including dealing with environmental heterogeneities, fluctuations and local sensing) can be of use in design and control of mobile systems on much smaller scales.
[1] Physics approaches to natural locomotion: Every robot is an experiment, Yasemin Ozkan Aydin, Jennifer M. Rieser, Christian M. Hubicki, William Savoie, Daniel I. Goldman, Chapter 6: Robotic Systems and Autonomous Platforms, 1st Edition, Advances in Materials and Manufacturing (2018) PDF
[2] A review on locomotion robophysics: the study of movement at the intersection of robotics, soft matter, and dynamical systems, Jeffrey Aguilar,Tingnan Zhang, Feifei Qian, Mark Kingsbury, Benjamin McInroe, Nicole Mazouchova, Chen Li, Ryan Maladen, Chaohui Gong, Matt Travers, Ross L. Hatton, Howie Choset, Paul B. Umbanhowar, and Daniel I. Goldman, Reports on Progress in Physics 79 110001 (2016) PDF
[3] Beneath our feet: strategies for locomotion in granular media, A.E. Hosoi and Daniel I. Goldman, Annual Review of Fluid Mechanics, 47, 431-453 (2015) PDF
[4] The effectiveness of resistive force theory in granular locomotion, Tingnan Zhang and Daniel I. Goldman, Physics of Fluids, 26, 101308 (2014) PDF
[5] Swimming in the desert, Yang Ding, Chen Li, and Daniel I. Goldman, Physics Today, November, pg. 68 (2013) PDF
Alain Goriely Filament motion through growth: principles and applications
For many biological systems, motion is limited or driven by growth. This is true for most plant motions as well as for the motion of axons in the early development of the brain. What are the guiding principles of motion through growth? It usually combines the relative motion of part of the body by addition of mass (apical or otherwise) for linear elongation controlled by active forces and the clever use of material anisotropy for the creation of curvature and torsion. In this talk, I will review these basic principles and see how they apply to different biological settings.
Stephanie Hoehn Morphogenesis is stressful - Mechanics of cell sheet folding in volvocalean algae
Living tissues are intelligent materials that can change their mechanical properties while they develop. In spite of extensive studies in multiple model organisms we are only just beginning to understand these dynamic properties and their role in tissue development. Although many tissues are known to exhibit visco-elastic properties, it is unclear which properties dominate three-dimensional shape changes of cellular monolayers, such as epithelia.
The embryonic inversion process in the micro-algal family Volvocales is uniquely suited for comparative studies on epithelial morphogenesis. Volvocalean embryos consist of cup-shaped or spherical cellular monolayers which invert their curvature in order to expose their flagella. These inversion processes involve a range of species-dependant complexity in terms of both the local cell shape changes and the resulting deformations of the cell sheet. Volvox globator exhibits one of the most striking processes of cell sheet folding: Through inwards folding along the equator the initially spherical cell sheet adopts a mushroom shape and eventually turns itself entirely inside-out [1]. A combination of light sheet microscopy and mathematical modelling revealed that the equatorial bending is complemented by active contraction in the posterior and expansion in the anterior hemisphere [2,3]. Laser ablation experiments are used to determine the role that the cell sheet’s elastic properties play in these deformations.
[1] Höhn S and Hallmann A. BMC Biology 9, 89 (2011)
[2] Höhn S, Honerkamp-Smith AR, Haas PA, Khuc Trong P, and Goldstein RE. Physical Review Letters 114, 178101 (2015)
[3] Haas PA, Höhn S, Honerkamp-Smith AR, Kirkegaard JB, and Goldstein RE. PLOS Biology 16, e2005536 (2018)
Jonathon Howard Curvature feedback coordinates axonemal dyneins to drive the flagellar beat in Chamydomonas
The snake-like beating patterns of sperm tails and the breast-stroke-like swimming strokes of ciliated organisms are driven by the molecular motor dynein. This motor protein generates sliding forces between adjacent microtubule doublets within the axoneme, the motile cytoskeletal structure within cilia and flagella. To create regular, oscillatory beating patterns, the activities of the dyneins must be coordinated, both spatially and temporally. It is thought that coordination is mediated by stresses or strains that build up within the moving axoneme, but it is not known which components of stress or strain are involved, nor how they feed back on the dyneins. To answer this question, we have measured the beating patterns of isolated, reactivate axonemes of the unicellular alga Chlamydomonas reinhardtii [1]. We compared the measurements in wild-type and mutant cells with models derived from different feedback mechanisms. We found that regulation by changes in axonemal curvature was the only mechanism that accords with the measurements [2]. We suggest that distortions due to bending of twisted axonemes may provide a mechanism by which the motors sense curvature [3]. To facilitate modeling studies of axonemal beats, we have published a simplified version of our model [4].
[1] Geyer, V. F., Sartori, P., Friedrich, B. M., Jülicher, F., & Howard, J. Current Biology 26, 1098–1103 (2016)
[2] Sartori, P., Geyer, V. F., Scholich, A., Jülicher, F., & Howard, J. eLife, 5, 343 doi.org/10.7554/eLife.13258 (2016)
[3] Sartori, P., Geyer, V. F., Howard, J., & Jülicher, F. Physical Review E, 94.042426 (2016)
[4] Geyer, V. F., Sartori, P., Jülicher, F., & Howard, J. In Dyneins (1st ed., Vol. 32, pp. 192–212). Academic Press. (2017)
Cecilia Laschi Lessons from nature and soft robotics: what an octopus can teach to roboticists
Largely inspired by the observation of the role of soft tissues in living organisms [1], the use of soft materials for building robots is recognized as one of the current challenges for pushing the boundaries of robotics technologies [2] and building robots for service tasks in natural environments. The study of living organisms sheds light on principles that can be fruitfully adopted to develop further robot abilities [3], as they exploit soft tissues and compliant structures to move effectively in complex natural environments [4]. The octopus is an excellent model for this [5] and provides principles for locomotion [6], swimming, and manipulation. While in robotics soft bodies pose important challenges for modelling and for controlling their behavior, at the same time living organisms like the octopus provide principles that can help soft robot control [7].
[1] S. Kim, C. Laschi, B. Trimmer, “Soft robotics: a bioinspired evolution in robotics”, Trends in Biotechnology, No.31, 2013, pp.287-294.
[2] C. Laschi, M. Cianchetti, “Soft Robotics: New Perspectives for Robot Bodyware and Control”, Frontiers in Bioengineering and Biotechnology, No.2, 2014
[3] C. Laschi, M. Cianchetti, B. Mazzolai, “Soft robotics: Technologies and systems pushing the boundaries of robot abilities”, Science Robotics 1(1), 2016.
[4] C. Laschi; B. Mazzolai, "Lessons from Animals and Plants: The Symbiosis of Morphological Computation and Soft Robotics", IEEE Robotics and Automation Magazine 23(3), 2016.
[5] C. Laschi, “Robot Octopus Points the Way to Soft Robotics With Eight Wiggly Arms”, IEEE Spectrum 1, 2016.
[6] M. Calisti, G. Picardi, C. Laschi, “Fundamentals of soft robot locomotion”, Journal of The Royal Society Interface 14(130), 2017
[7] T. George Thuruthel, Y. Ansari, E. Falotico, C. Laschi, “Control Strategies for Soft Robotic Manipulators: A Survey”, Soft Robotics 5(2), 2018, pp.149-163.
Amos Maritan Optimality and scaling in living systems and ecological communities
Forests are terrestrial ecosystems with a high degree of structural and functional diversity: in the tropics, there often are hundreds of coexisting plant species with different habitats and thousands of consumers, each of them with interspecific relationships with plant species. This leads to a multitude of interconnected food webs and complex fluxes of matter and energy. We demonstrate an astounding simplicity underlying the apparent bewildering complexity of forests. Our starting point is based on an optimization principle for understanding and making predictions that are in accord with empirical data. The simplicity originates from the well-known empirical observation that power law relationships, also known as allometric scaling, are pervasive in tree communities and, more in general, in complex ecological communities.
Cristian Micheletti Knotted DNA: conformational, dynamical and pore-translocation properties
Knots and supercoiling are both introduced in bacterial plasmids by catalytic processes involving DNA strand passages. I will report on a recent study where we used molecular dynamics simulations and a mesoscopic DNA model, to study the simultaneous presence of knots and supercoiling in DNA rings and the kinetic and metric implications which may be relevant for the simplifying action of topoisomerases [1]. Finally, I will discuss how the same modelling and simulation approach [2] can be used shed light on the complex experimental phenomenology of knotted DNA translocating through solid state nanopores [3].
[1] L. Coronel, A. Suma and C. Micheletti Dynamics of supercoiled DNA with complex knots Nucleic Acids Res., 2018, 46 , 7533 .
[2] A. Suma and C. Micheletti Pore translocation of knotted DNA rings Proc. Natl. Acad. Sci. USA, 2017, 114 , E2991-E2997.
[3] Plesa C, et al. Direct observation of DNA knots using a solid-state nanopore. Nat Nanotechnol (2016) 11:1093–1097.
Paolo Netti Cell instructive materials to control and guide cell locomotion
Cell migration is a crucial aspect of diverse biological events including morphogenesis, tissue repair and homeostasis [1]. Specifically engineered culturing platform demonstrated that several biochemical and biophysical signals strongly affect cell migration [2]. In particular, patterns of topographic, mechanical or biomolecular signals proved to exert a strong control over cell adhesion and cell generated forces that fundamentally govern motility, both at a single cell or collective level [3]. In this presentation, strategies aimed at encoding signals constituting sets of instructions that regulate cell adhesion, cell mechanics and migration will be illustrated. Particular emphasis will be given on the interface between cells and material, the locus in which cells recognize and respond to adhesion signals and patterns thereof. Signals presented at different length scales (nano-, submicron- and micron-scale) target different cell compartments and can differently affect cell adhesion, orientation and migration [4,5]. Finally, examples on how cell generated forces and motility may be exploited to sculpt tissue shape and microarchitecture will be presented and discussed [6].
This talk aims at highlighting the central role of material signals, which – if sapiently organized – may dictate cell fate and functions through the surface-adhesion-cytoskeleton axis.
[1] Trepat X, Chen Z, Jacobson K. Cell migration. Compr Physiol. 2, 2369-92, 2012.
[2] Ventre M, Causa F, Netti PA. Determinants of cell-material crosstalk at the interface: towards engineering of cell instructive materials. J R Soc Interface. 9, 2017-32, 2012
[3] Ventre M, Netti PA. Engineering Cell Instructive Materials To Control Cell Fate and Functions through Material Cues and Surface Patterning. ACS Appl Mater Interfaces. 8, 14896-908, 2016
[4] Ventre M, Natale CF, Rianna C, Netti PA. Topographic cell instructive patterns to control cell adhesion, polarization and migration. J R Soc Interface. 11, 20140687, 2014.
[5] Natale CF, Ventre M, Netti PA. Tuning the material-cytoskeleton crosstalk via nanoconfinement of focal adhesions. Biomaterials 35, 2743-51, 2014.
[6] Iannone M, Ventre M, Formisano L, Casalino L, Patriarca EJ, Netti PA. Nanoengineered surfaces for focal adhesion guidance trigger mesenchymal stem cell self-organization and tenogenesis. Nano Lett. 15, 1517-25, 201
Bernhard Schrefler Modeling drug delivery and efficiency in the tumor microenvironment
Computational Transport Oncophysics [1] provides the computational tools which, together with imaging, analysis and quantification, will contribute to rationalize the delivery of therapeutic agents and to evaluate their efficiency, forming an oncophysical modeling framework. This framework should comprise a tumor growth model within the local tumor environment, coupled with a patient specific biodistribution model. For the first one we present a very general multiphase flow model in an extracellular matrix (ECM), dealt with as a deforming porous solid which may undergo remodeling; it comprises three fluid phases, i.e. tumor cells (TCs), divided into living and necrotic cells, healthy cells (HCs) and interstitial fluid (IF). The IF transports chemical species such as tumor angiogenic factor (TAF), nutrients and therapeutic agents. Transport of these species within extravascular space takes place by convection and diffusion. Coopted blood vessels are included as line elements with blood flow exchanging nutrients and therapeutic agents with the IF. Angiogenesis is represented by the blood vessel density (density of newly created endothelial cells). The model accounts not only for growth and necrosis but also for migration of cells through the ECM, for different stiffness of the cell population with respect to the ECM, build-up of cortical tension between healthy and tumor tissues and possible invasion of the tumor tissue by the healthy tissue or vice versa, mediated by these cortical tensions. Further it allows for modeling lysis, adhesion of the cells to their ECMs, adhesion among cells and possible detachment as well as the effects of drugs. For a fast evaluation of the drug effects also a simpler bi-phasic model with cells and ECM lumped together, but permeated by an IF, may be used; it excludes however several of the above mentioned features. Examples for both models will be shown.
[1] Michor, F., J. Liphardt, M. Ferrari, and J. Widom, What does physics have to do with cancer? Nature Reviews Cancer, 2011. 11(9): p. 657-670.
Eran Sharon Propagating chemical waves as an engine for autonomous flapping sheets
Autonomous actuation of soft tissues is common in a wide variety of natural systems, both on cellular and macroscopic scales. The success in mimicking such systems in manmade structures is limited. We present an autonomous shape-transforming sheet and suggest a framework for its quantitative analysis and design.
Thin sheets made of NIPA- Ruthenium copolymer gel are placed in a solution of the Belousov-Zhabotinsky (BZ) reactants, leading to the spontaneous periodic propagation of chemical fronts within the gel. These front lead to local contraction and expansion of the gel, driving its periodic buckling into 3D evolving shapes. Using the theory of incompatible elastic sheets, we describe the system as an evolving non-Euclidean plate. The reference metric of the plate varies in time and space according to the BZ field evolution. We obtain a connection between the BZ field and the 3D configurations and confirm it experimentally.
Roman Stocker Microbial motility in the ocean
Although we now know that microorganisms rule the oceans - controlling productivity and biogeochemical cycles - we largely ignore how they are affected by typical fluid flow conditions. For example, microbes are routinely exposed to turbulence, yet physicists have ignored microbes and biologists have ignored turbulence. Here I present microfluidic and millifluidic experiments, combined with mathematical models, to show that fluid flow can have profound effects on the biomechanics and the ecology of swimming microorganisms. I illustrate this through a series of examples, and will focus in particular on 'gravitaxis', the tendency of many phytoplankton species to swim along the direction of gravity. I will show that, in the presence of flow, gravitaxis results in intense clustering of cells in layers and patches, akin to those often observed by oceanographers, which can have profound effects on plankton population dynamics. Intriguingly, plankton seem to 'know fluid mechanics' and I will present recent evidence that they are able to actively evade turbulence by sensing the simplest among the cues inherent in small-scale turbulent eddies. In addition to representing a new class of active particle problems that promises to keep the fluid mechanician busy for some time to come, these processes are environmentally important because they affect the ecological dynamics and biogeochemical consequences of some of the most important players in aquatic ecosystems.
Julia Yeomans Self-propelled topological defects in active matter
Active materials, such as bacteria, molecular motors and self-propelled colloids, are Nature’s engines. They continuously transform chemical energy from their environment to mechanical work. Dense active matter shows mesoscale turbulence, the emergence of chaotic flow structures characterised by high vorticity and self-propelled topological defects.
The chaotic nature of active turbulence means that it is likely to be difficult to harness its energy. Hence it is interesting to consider ways to `tame' active turbulence, channeling the energy input into coherent flows. This can be done by screening hydrodynamics through confinement or friction, and I will describe flow patterns and defect trajectories in active matter in confined geometries.
Moreover the ideas of active matter suggest new ways of interpreting cell motility and cell division. In particular recent results indicate that active topological defects may help to regulate turnover in epithelial cell layers and contribute to controlling the structure of bacterial colonies.