1st BioSoft symposium Biophysical approaches to understand life at different scales Forschungszentrum Jülich ± 6th November 2014 Within the scope of the graduate school program International Helmholtz Research School in Biophysics and Soft Matter (IHRS BioSoft), the fellows are pleased to organize the first networking event. We hope that our efforts help to foster a series of events in the near future. This meeting brings together researchers using quantitative approaches towards the biophysical understanding of different physiological processes essential to life. The sheer complexity of living organisms poses a jumbled puzzle to solve when studying processes like the development of an early embryo or the maturation of pathogenic behaviors. Recent developments in biotechnology, molecular biology, biochemistry and biophysical modeling have fostered unprecedented approaches to unravel the multidimensional facets of such complex pathways. Our workshop aims at providing an interdisciplinary platform to bring together the complementary skills of experimentalists and theoreticians (spanning as many involved fields as possible) in order to understand the role of forces, flow and fluctuations within biological systems. The 7 proposed talks specifically address 3 major themes: 1. Bioadhesion, cytoskeleton and cell motility 2. Tissue growth and morphogenesis 3. Collective behaviors in biological networks The proposed themes focus on cellular behavior at different scales ranging from the single cell level to multicellular-aggregates like tissues, and even encompass complex biological networks. A major goal is to provide a platform for students and young scientists to present and discuss their work with other students and expert researchers, in order to promote the mutual exchange of ideas and facilitate the development of novel research directions. Looking forward to seeing in Juelich, Sabyasachi Dasgupta, Guglielmo Saggiorato, Gloria Fabris, and Melanie Balbach Schedule 9:00 - 9:10 Introduction to the symposium 9:10 - 10:05 Biomimetics (T1) A. Roux ± Univ. of Geneva (Switzerland) Mechanics of protein coats in cell membrane traffic 10:05 - 11:00 Cytoskeleton (T2) J. Guck - TU Dresden (Germany) How cells feel - and why that©s important 11:00 - 11:15 Coffee & tea break 11:15 - 12:15 Cell Adhesion (T3) E. Sackmann - TU München (Germany) Physics of Cell Adhesion 12:15-14:15 Poster Session @ Lunch 14:15 - 15:15 Collective Behavior (T4) P. Silberzan - Institut Curie, Paris (France) Imposing and releasing confinement to an epithelium 15:15 - 16:15 Bionetworks (T5) T. Mora - ENS, Paris (France) Inferring the statistical mechanics of collective phenomena 16:15 - 16:45 Coffee & tea break 16:45 - 17:45 Morphogenesis (T6) P. F. Lenne - IBDM, Marseille (France) Mechanics of cell contacts during tissue morphogenesis 17:45 - 18:45 Developmental Biology L. Hufnagel - EMBL Heidelberg (Germany) (T7) BioImaging across scales with light-sheet microscopy: from cells to embryos 18:45 - 19:00 Valedictory remarks Talk abstracts T1. Aurelien Roux Mechanics of protein coats in cell membrane traffic Proteins involved in membrane traffic transiently interact with lipid membranes in order to remodel them, i.e. to deform them, cut and fuse them. But lipid membrane are not passive in these processes, they are visco-elastic surfaces which require energy to be remodeled. In this talk I will review a few studies where we show that the elastic energy of the membrane impacts the function of protein assemblies in membrane traffic. In particular, we will show how membrane tension and rigidity competes with clathrin budding and dynamic fission reactions, and I will show how ESCRT proteins have evolved to deform membranes by buckling. T2. Jochen Guck How cells feel - and why that©s important While most current biological research focuses on molecular, biochemical aspects of cell function, we are interested in the mechanical properties of cells and tissue and their importance for biological function. The mechanical strength of cells is largely determined by the cytoskeleton, an internal polymer hybrid network intricately regulated by many signaling pathways. This cytoskeleton evolves during physiological changes, such as differentiation, is involved in many cellular functions, such as migration, and is characteristically altered in pathologies, including cancer or inflammation. We can exploit the deformability of the cytoskeleton as a link between molecular structure and biological function to sensitively monitor these functional changes using an optical stretcher and a novel, high-throughput microfluidic technique. Our results indicate that the material properties of cells define their function, can be used as an inherent cell marker and could serve as target for novel therapies. T3. Erich Sackmann Physics of Cell Adhesion Cells migrate by ongoing formation of adhesion domains at the leading front and their dismantling at the trailing end. Protruding forces are generated by sequential generation of solitary actin gelation waves protruding form adhesion domains (AD). The AD are formed by interplay of generic and specific interfacial forces and act both as force transmitting feet and biochemical reaction centers controlling actin polymerization and actin-microtubule crosstalk. Actin polymerization serves the generation of protrusion forces while microtubules drive the motion of the cell body. The global polarization of migrating cells is mediated by actin microtubule crosstalk. The short range cell polarization is controlled by the competition of antagonistic GTPase controlled biochemical pathways. that promote actin gelation at the front of migrating cells and AD dismantling at the trailing ends , respectively. Insight into the actin microtubule crosstalk is gained by magnetic tweezer micro-rheometry. Microinterferometry (RICM) serves the observation of adhesion domains and the measurement of adhesion and transmission forces. T4. Pascal Silberzan Imposing and releasing confinement to an epithelium Epithelial tissues, for which cells maintain contacts with their neighbors, exhibit collective behaviors largely controlled by cell-cell interactions. In this context confinement and boundary conditions play an important role in the dynamics of these cell assemblies. Interestingly, many in vivo processes, including morphogenesis or tumor maturation, involve small populations of cells within a spatially restricted region. Cells confined on finite, population-sized domains exhibit both collective rotation with stochastic reversals and low-frequency radial displacement modes. When this boundary condition is removed, we observe the collective migration of these epithelia. In the first stages, the essential characteristics of these collective dynamics in these two situations are well described by the same model in which cells are described as persistent random walkers which adapt their motion to that of their neighbors. However, at late stages, cells in confined epithelia develop a tridimensional structure in the form of a peripheral cell cord at the domain edge. Epithelial confinement by itself is thus observed to induce morphogenetic-like processes including spontaneous collective pulsations and transition from 2D to 3D. References: [1] Deforet, M., Hakim, V., Yevick, H. G., Duclos, G. & Silberzan, P. Emergence of collective modes and tridimensional structures from epithelial confinement. Nat. Commun. 5, 1±9 (2014). [2] Reffay, M. et al. Interplay of RhoA and mechanical forces in collective cell migration driven by leader cells. Nat. Cell Biol. 16, 217 (2014). [3] Sepúlveda, N. et al. Collective cell motion in an epithelial sheet can be quantitatively described by a stochastic interacting particle model. PLoS Comput. Biol. 9, e1002944 (2013). T5. Thierry Mora Inferring the statistical mechanics of collective phenomena Collective phenomena are emergent events that cannot simply be explained as a sum of individual behaviors. They are relevant at many scales in biology, from the collective dynamics of neural networks to the concerted motion of bird flocks. Focusing on these two examples, I will show how the tools and concepts of statistical mechanics, when applied directly to experimental data, can be used to gain insight about the collective behavior of complex biological systems. T6. Pierre - François Lenne Mechanics of cell contacts during tissue morphogenesis Cell-generated forces produce a variety of tissue movements and tissue shape changes. The cytoskeletal elements that underlie these dynamics act at cell-cell and cell-extracellular matrix contacts to apply local forces on adhesive structures. Using quantitative imaging and force measurements in vivo, we study how cell-cell contacts are organized and how subcellular tensile forces are transmitted to drive tissue morphogenesis. T7. Lars Hufnagel BioImaging across scales with light-sheet microscopy: from cells to embryos Developmental processes are highly dynamic and span many temporal and spatial scales. A whole-embryo view of morphogenesis with subcellular resolution is essential to unravel the interconnected dynamics at the varying scales of development, from interactions within cells to those acting across the whole embryo. Bridging scales from the submicron to the millimeter range with a temporal resolution of several seconds (combined with a total imaging time of several hours) not only poses tremendous challenges for modern microscopy methods but also requires powerful computational approaches for data handling, processing