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Paris Biological Physics
Community Day 2020

Thursday 12th and Friday 13th November 2020 @ 2pm
Online Zoom meeting

The Paris Biological Physics Community Day (PBPCD 2020) is a conference organized for and by young researchers. In keeping with the times, the 2020 edition will be held online, which allows participants from all around the world to join us. In the program the talks of the invited speakers are interleaved with short presentations by young researchers. For any questions, contact us on social networks: Facebook, Twitter.

Abstract submission is now closed.

If you want to attend the meeting through zoom, please register here.

Keynote Speakers

Program

Thursday November 12th

13h45 - 14h00 Opening of the online room
14h00 - 14h30
  • Pere Roca-Cusachs

    Mechanochemistry of cell membrane responses to stretch

    Cells in physiological conditions are often submitted to mechanical forces, to which they respond both by adapting their shape, and by triggering active responses. By using a model system of stretch, here I will discuss the role of the plasma membrane in both types of responses. I will show that initial membrane adaptation to stretch is explained by a purely passive mechanical process leading to membrane deformation, which is then followed by an active process to restore membrane homeostasis. This active process involves membrane reshaping by BAR-domain proteins and actin, employing a fascinating mechanochemical feedback that can be understood by an isotropic to nematic transition. This transition is defined both in terms of chemistry (protein order) and mechanics (membrane shape). The resulting phenomenon enables a new mode of mechanotransduction, by which mechanically-induced membrane deformation triggers BAR-mediated processes, with potential implications in several biological scenarios.

14h30 - 15h30
  • Juan Manuel Garcia Arcos Institut Curie

    Stabilization and motility mechanism of blebs

    Context & Objectives
    Previously associated with apoptosis, blebs have arisen in the past decade as important structures for amoeboid cell migration, particularly for cancer cells. Amoeba, choanoflagellates, and mammalian cells form large and stable blebs in cells under non-adhesive confinement. Unlike previously described blebs, they do not retract and stabilize a constant cortical actin flow, which leads to cell migration. The goal of the project is to understand the mechanisms for bleb stabilization and the emergence of retrograde flow and migratory behavior.
    Results We propose a working model for bleb morphogenesis in which the final phenotype (retractile or stable bleb) is due to the relative timing of cortex formation versus myosin contraction. Only if the contraction happens before the cortex has completely formed, the bleb will go into a steady-state recapitulating the dynamics of polarized confined cells, forming actomyosin gradients due to a sustained retrograde flow. After formation, stable blebs can transition between phases of retraction or stabilization depending on the interaction between the contracting base of the bleb and the front membrane. In persistent blebs, there is a mechanical uncoupling between the actin filaments and the membrane at the front. Weakening actin-membrane links or depleting actin from the bleb front increased the fraction of persistent blebs. Our results present a negative role of actin-membrane attachment in protrusion persistence, contributing to recent findings in the field. We identified three cortical regimes in persistent blebs: I) a contractile cortex at the base of the bleb, enriched in NMIIA, with actin network disassembly; II) a crosslinked cortex, in the middle region, that transduces the forces from the base to the bleb front but does not contract; and III) a loose cortex at the bleb front, composed of single filaments poorly attached to the membrane or small actin clusters with a gas-like behavior.

    Conclusion & Persectives
    These cortex regimes are reminiscent of the force percolation dynamics of in vitro reconstituted contractile actin networks but have not yet been observed in a living system. Even in in vitro systems, experiments have not yet been able to link percolation regimes to the density of filaments at the molecular level. The description of a cellular process explained by percolation theory at a molecular level constitutes a novel contribution to the cell biophysics and cytoskeleton field.

  • David Brückner LMU Munich

    Learning the dynamics of cell-cell interactions in confined cell migration

    How do we describe the stochastic dynamics of colliding cells in a unifying quantitative framework? Such cell-cell interactions play a key role in shaping the stochastic trajectories of migrating cells in physiological processes. However, a framework to describe the stochastic dynamics of interacting cells in remains elusive. Here, we experimentally monitor stochastic cell trajectories in a minimal cell collider: a dumbbell-shaped micropattern on which pairs of cells perform repeated cellular collisions. We observe different characteristic behaviors, including cells reversing, following and sliding past each other upon collision. Capitalizing on this large experimental data set of coupled cell trajectories, we apply a statistical learning approach to infer an interacting stochastic equation of motion that accurately predicts the observed interaction behaviors. Our approach reveals that interacting non-cancerous MCF10A cells can be described by repulsion and friction interactions. In contrast, cancerous MDA-MB-231 cells exhibit novel and surprising attraction and anti-friction interactions, promoting the predominant relative sliding behavior observed for these cells. Based on these experimentally inferred interactions, we show how this framework may generalize to provide a unifying theoretical description of the diverse cellular interaction behaviors of distinct cell types.

  • Alexander Chamolly LPENS Université PSL

    Direct vs indirect hydrodynamic interactions during bundle formation of bacterial flagella

    Most motile bacteria swim in viscous fluids by rotating multiple helical flagellar filaments. These semi-rigid filaments repeatedly join (‘bundle’) and separate (‘unbundle’), resulting in a two-gait random walk-like motion of the cell. In this process, hydrodynamic interactions between the filaments are known to play an important role and can be categorised into two distinct types: direct interactions mediated through flows that are generated through the actuation of the filaments themselves, and indirect interactions mediated through the motion of the cell body (i.e. flows induced in the swimming frame that result from propulsion). To understand the relative importance of these two types of interactions, we first study a minimal singularity model of flagellar bundling. Using hydrodynamic images, we solve for the flow analytically and compute both direct and indirect interactions exactly as a function of the length of the flagellar filaments and their angular separation. We show (i) that the generation of thrust by flagella alone is sufficient to drive the system towards a bundled state through both types of interaction in the entire geometric parameter range; (ii) that for both thrust- and rotation-induced flows indirect advection dominates for long filaments and at wide separation, i.e. primarily during the early stages of the bundling process; and (iii) that, in contrast, direct interactions dominate when flagellar filaments are in each other’s wake, which we characterise mathematically. We further introduce a numerical elastohydrodynamic model that allows us to compute the dynamics of the helical axes of each flagellar filament while analysing direct and indirect interactions separately. With this we show (iv) that the shift in balance between direct and indirect interactions is non-monotonic during the bundling process, with a peak in direct dominance, and that different sections of the flagella are affected by these changes to different extents.

  • Antoine Fruleux LadHyX Polytechnique

    Cellular Fourier Transform: a new approach to analyse living tissues at multiple scales

    Many questions in Biology concern the relation between different scales (i.e. sub-cellular, cellular or supra-cellular). For example, organ development often gives rise to robust sizes and shapes, in striking contrast with the variability observed at a cellular scale. In a classical physical context, many tools exist to investigate the relation between scales such as Fourier Transforms or wavelet decomposition but they are not well suited to biological tissues. In biological tissues, cells set a reference scale at which parameters and fields reflecting material properties and state are often assessed and space discretization based on standard coordinate systems is not commensurate with the natural discretization into geometrically disordered cells. We built a method, which we call Cellular Fourier Transform (CFT), to analyze cellular fields, which includes both discrete fields defined only at cell level and continuous fields smoothed out from their sub-cell variations. During my presentation, I will introduce this method and discuss its application to the growth of floral organs.

15h30 - 16h00 Virtual Coffee Break
16h00 - 16h30
  • Jacqueline Tabler

    Cellular behaviors driving mammalian skull morphogenesis

    A common feature in morphogenesis is anisotropic growth, where tissues do not grow equally in all directions. However, the cellular and physical cues that drive anisotropy in vertebrate tissues are poorly understood, especially in mesenchyme that lack the cell-cell and cell-substrate interactions that instruct morphogenesis in epithelial tissues. Here, we present the embryonic skull cap as a novel model for studying the cellular behaviors driving anisotropic growth in an intact mesenchymal tissue. By tracking osteoblast nuclei ex vivo, we find that anisotropic expansion of frontal bones is driven by both intrinsic and extrinsic growth mechanisms. While we find that oriented divisions contribute to intrinsic growth of the bone, these divisions generate anisotropic expansion through biased displacement of daughter cells and limited neighbor exchange. Additionally, and contrary to previous reports, we find extrinsic bone growth that is driven by the progressive spatial and temporal pattern of differentiation in undifferentiated mesenchyme at the growing edge of the bone. Together, these data suggest that cell displacement and spatiotemporally controlled differentiation co-operate to drive anisotropic bone expansion. Our system is the first live imaging platform to offer subcellular resolution of osteoblasts during skull morphogenesis that could be used to identify fundamental mechanisms regulating shape generation in mesenchymal tissues.

16h30 - 17h30
  • Alexandros Glentis IJM Université Paris-Diderot

    Curved surfaces induce cohesive whole-tissue epithelial rotation

    During embryonic and glandular development, epithelial cells adapt a persistent, collective rotational movement. While this has been shown to be important for overall tissue elongation and polarization, little is known about the underlying mechanisms and the interactions between the cells and their curved substrates. Here, to mimic the in vivo epithelial dynamics, we first embedded single MDCK cells in 3D Matrigel and observed that they spontaneously form tubular cysts which, upon mitosis seizure, cohesively rotate for hours. To study in detail the dynamics of rotating epithelia, we induce cohesive whole-tissue rotations by growing MDCK epithelia on micro-fabricated tubes of various curvature degrees. Our findings suggest that collective rotation depends on the extent of tubular curvature, cell polarity and cell-cell junctions stability. Cells adapt their actin cytoskeleton organization in respect to the underlying curvature to rotate cohesively on both positive and negative curvatures. We also report that during coordinated rotation, cells exert a lesser load of forces on their substrate compared non-coordinated cell movement states. Altogether, our results indicate that surface curvature regulates collective cell migration, underlining the effect of geometry on tissue dynamics and could induce further insights into in vivo multicellular motions.

  • Xiuyu Wang LadHyX Polytechnique

    Contractility-induced self-organization of smooth muscle cells: from multilayer cell sheets to dynamic clusters

    Smooth muscle cells (SMCs) are mural cells that constitute the medial layer of various hollow organs. Aberrant SMC organization is the hallmark of many diseases including atherosclerosis, hypertension, asthma, and uterine fibroids. In studies on SMC organization, we observed that cells plated on flat substrates spontaneously aggregate into three-dimensional clusters once the cell seeding density is sufficiently high. We conceptualize this process as consisting of five phases: opening of a hole in the cellular layer, cellular aggregation and aggregate growth, aggregate tear-off from the underlying substrate, and aggregate rounding-up into a stable cluster. For each of these phases, we have combined experiments and physical modeling to gain insight into the governing mechanisms and dynamics. Our models rely on the analogy between cellular aggregates and wetting phenomena of liquid droplets. We model individual SMC clusters as active liquid droplets characterized by an effective surface tension (arising from cell contractility and intercellular adhesion), an internal viscosity, and friction with the substrate. This active liquid droplet model allows us to explain the observed dynamics of: 1) hole formation, analogous to brittle viscoelastic fracture followed by dewetting, 2) cluster shape evolution, analogous to droplet round-up, and 3) cluster fusion, analogous to droplet coalescence. The model predictions are in agreement with the experimental observations and provide estimates of material properties of SMC clusters. By comparing the model results to our in vitro experiments, we conclude that clusters form when SMC density exceeds a critical threshold for contraction forces to overcome adhesion forces to the substrate.

  • Irène Nagle MSC Université Paris-Diderot

    Magnetic muscular cells to develop an engineering tool at tissue scale: the magnetic stretcher

    Skeletal muscle is one of the most abundant tissue type in the human body. It is a multi-scale structure with a very complex organization. It consists of aligned bundles of muscle fibers composed of entangled myofibers, or single muscle fibers, that originate from the fusion of hundreds of muscle precursor cells, the myoblasts. Creating in vitro models for the skeletal muscle would offer a polyvalent platform for fundamental studies in tissue biology but also for the development of new drugs or gene therapies to treat muscular diseases or traumatisms. However, reproducing the geometry and the function of muscle is still a real challenge. Muscle containing also a low amount of extracellular matrix, there is a need to develop a technology without any substrate able to reproduce this 3D organization while enabling the application of forces to obtain muscle functionalization.

    The use of magnetic fields and forces can be a solution. By incorporating superparamagnetic iron oxide maghemite (γ-Fe2O3) nanoparticles to the cells, we can confer them, without altering their biological properties, magnetic properties and therefore enable cell manipulation. The magnetic labelling was applied to the immortalized mouse myoblast cell line C2C12 to obtain a stimulable aggregate without any support matrix. A cell-only multicellular aggregate of myoblasts between two mobile magnets (magnetic stretcher) was successfully obtained and mechanically stimulated in the device for several days. This magnetic stretcher represents a new tool to study cell differentiation.

    Model muscular tissues are interesting to investigate mechanical properties of muscle cells and to decipher the influence of microscopic cell properties at the level of tissue mechanics. Using a magnet to flatten multicellular myoblast spheroids, we explored the role of actin cytoskeleton organization, cell-cell adhesions as well as acto-myosin contractility on the surface tension and the Young modulus of this model tissue. Besides, the influence of the intermediate filaments architecture was investigated by looking at desmin-mutated myoblasts. Desmin disorganization (protein aggregation in mutants) was proven to be responsible for an increase of both surface tension and rigidity, enhancing the fundamental role of the architecture of intermediate filament network in this 3D model tissue.

  • Hugo Le Roy LPTMS Université Paris-Saclay

    Elastic frustration in self assembling system leads to fiber formation

    Self-organization is essential for keeping living organism functional. Any mistake leads to severe disease such as Alzheimer. In this case, protein that are usually soluble start aggregating leading to fibril structures that are incompatible with the initial biological role of the protein. We try to understand this tendency that a wide variety of protein exhibit using a very general mechanism. Indeed, if on the one hand a surface tension energy would drive the aggregation, on the other hand, because of their ill fitting shape, proteins would need to deform to do so, which has a cost of elastic energy. Fiber like aggregate would therefore be a trade of between those two energies. Previous studies have already found that fiber like aggregate can have an energetic benefit over other shape, but here we investigate, using statistical physics tools, the thermodynamic properties of such fibers.

17h30 - 18h00 Virtual cocktail

Friday November 13th

13h45 - 14h00 Opening of the online room
14h00 - 14h30
  • Oded Rechavi

    C. elegans parental experiences regulate a critical decision made by the progeny

    C. elegans can transmit certain responses transgenerationally, however it is unknown whether these can impact the process of evolution. Here, by studying nematodes that choose whether to self-reproduce or outcross, we show that inherited small RNAs affect sexual attraction and mating for multiple generations and thus indirectly control genetic variation. Further, stress leads to enhanced sexual attraction which transmits transgenerationally for three generations. Simulations and multigenerational competition experiments demonstrate that the rise in mating, driven by heritable small RNAs that promote sexual attraction, can increase alleles frequencies in the population. This non-DNA based inheritance process could be a mechanism for elevating the rate of outcrossing in challenging environments, when increasing genetic variation is advantageous.

14h30 - 15h30
  • Simone Pompei IFOM Milan

    Drug-induced colorectal cancer persister cells show increased mutation rate

    The emergence of drug resistance is a major limitation to the efficacy of anti-cancer targeted therapies. Drug-resistant mutants that are not present when therapy is initiated may derive from sub-populations of drug-tolerant persister cells, which are known to survive treatment for extended period of time. Whether persister cancer cells pre-exist therapeutic stress or are drug-induced is unclear. Additionally, persister cells can transiently compromise fidelity of DNA replication, but it remains unknown if the mutation rate concomitantly and quantitatively increases. Here, by combining mathematical modeling and experimental characterization, we show that in colorectal cancer, persister cells are induced by, and do not predate, drug treatment. We then establish a two-step fluctuation assay generalizing the test originally developed by Luria and Delbrück, to measure mutation rates of tumor cells. We find that colorectal cancer persister cells show a 10- to 100-fold increase of their mutation rate when exposed to clinically approved therapies. Taken together, our results provide a quantitative and predictive framework that could be used to design strategies to restrict therapeutic tolerance and resistance in tumors. The mathematical framework we developed could be broadly used to assess how environmental conditions affect mutability in mammalian cells.

  • Vasyl Alba Northwestern University

    Dimensionality-deduction in the drosophila wing as revealed by landmark-free measurements of phenotype

    Organismal phenotypes emerge from a complex set of genotypic interactions. While technological advances in sequencing provide a quantitative description of an organism’s genotype, characterization of phenotypes lags far behind. Here, we relate genotype to the complex and multi-dimensional phenotype of an anatomi-cal structure using the Drosophila fly wing as a model system by developing a mathematical approach that enables a robust description of biologically salient phenotypic variation. Analysing natural phenotypic varia-tion, and variation generated by perturbations in genetic and environmental conditions during development, we observe a highly constrained set of wing phenotypes. In a striking example of dimensionality reduction, the nature of varieties produced by the fly’s developmental program is constrained to a single integrated mode of variation in the wing. Our strategy demonstrates the emergent simplicity manifest in the genotype to phenotype map in the Drosophila wing and may represent a general approach for interrogating a variety of genotype-phenotype relationships.

  • Clara Moreno-Fenoll LGE ESPCI Université PSL

    Single-cell imaging of pseudomonas reveals dynamic localisation of the extracellular iron-scavenger pyoverdin

    Extracellular products perform important functions in microbial communities, such as protection (biofilms), coordinated action (quorum sensing), and access to recalcitrant nutrients (secreted enzymes). Pyoverdin is a soluble diffusible metal chelator synthesized by Pseudomonas to enable internalization of otherwise insoluble iron. It binds iron in the external medium and delivers it to the bacterial periplasm. While previously thought to be equally available to all members of a population, recent studies challenge this assumption. In Pseudomonas aeruginosa microcolonies, pyoverdin preferentially diffuses between adjacent cells, thus reducing its loss into the environment. Cells have been found to tune the intracellular concentration of pyoverdin in response to oxidative stress. Furthermore, pyoverdin-producing cells can retain a fitness advantage in conditions where non-producing cells should be favored. Together this points to a significant control of pyoverdin distribution. Using time-lapse fluorescence microscopy to track single cells in growing microcolonies of Pseudomonas fluorescens SBW25, we identify a novel phenotype that supports this notion: accumulation of pyoverdin at the cell pole. This phenotype is triggered by conditions that induce arrest of cell division. Our data lead us to propose a function for polarization in recovery of growth after stress. By analyzing relevant mutants we set the foundation for a thorough characterization of the mechanism. Finally, we provide some evolutionary and ecological context by exploring the presence of this phenotype in multi-species communities and related pseudomonads. This approach emphasizes the need to integrate different levels of complexity - from subcellular to population - as well as considering ecological and evolutionary constraints, to rigorously understand the role of extracellular products in bacterial populations.

  • Leonardo Pacciani-Mori LiPh University of Padua

    Constrained proteome allocation affects coexistence in models of competitive microbial communities

    Microbial communities are ubiquitous and play crucial roles in many natural processes. Despite their importance for the environment, industry and human health, there are still many aspects of microbial community dynamics that we do not understand quantitatively. Recent experiments have shown that the metabolism of species in a community is intertwined with its composition, suggesting that properties at the intracellular level such as the allocation of cellular proteomic resources must be taken into account when describing microbial communities with a population dynamics approach. Here we reconsider one of the theoretical frameworks most commonly used to model population dynamics in competitive ecosystems, MacArthur's consumer-resource model, in light of experimental evidence showing how proteome allocation affects microbial growth. This new framework allows us to describe community dynamics at an intermediate level of complexity between classical consumer-resource models and biochemical models of microbial metabolism, accounting for temporally-varying proteome allocation subject to constraints on growth and protein synthesis in the presence of multiple resources, while preserving analytical insight into the dynamics of the system. We study our consumer-proteome-resource model analytically and numerically to determine the conditions that allow multiple species to coexist in systems with arbitrary numbers of species and resources.

15h30 - 16h00 Virtual Coffee Break
16h00 - 16h30
  • Emma Hodcroft

    Real-time tracking for real-life pandemics: Nextstrain and SARS-CoV-2

    The emergence of SARS-CoV-2 has driven an enormous global effort to contribute and share genomic data in order to inform local authorities and the international community about key aspects of the outbreak. Analyses of these data have played an important role in tracking the epidemiology and evolution of the virus in real-time. Nextstrain (nextstrain.org) is an open science initiative to harness the scientific and public health potential of pathogen genome data, and has previously provided key insight into outbreaks of Ebola and Zika, and longer-term pathogen spread of Influenza and Enterovirus. It provides a continually-updated view of publicly available data alongside powerful analytic and visualization tools for use by the community. The Nextstrain team has been maintaining an up-to-date analysis of SARS-CoV-2 at nextstrain.org/ncov since 20 Jan 2020. In this talk, I'll discuss the realisation of 'real-time tracking' with SARS-CoV-2 and what genetic epidemiology has allowed us to uncover about the virus' spread. I'll also discuss some of the challenges Nextstrain has faced in processing and displaying large amounts of real-time data with unprecedented public attention, and how the move from 'global' to 'local' focus is presenting new challenges.

16h30 - 17h30
  • Rossana Droghetti IFOM Milan

    An evolutionary model identifies the main selective pressures for the evolution of genome-replication profiles

    Recent results comparing the temporal program of genome replication of yeast species belonging to the Lachancea clade support the scenario that the evolution of replication timing program could be mainly driven by correlated acquisition and loss events of active replication origins. Using these results as a benchmark, we develop an evolutionary model defined as birth-death process for replication origins, and use it to identify the selective pressures that shape the replication timing profiles. Comparing different evolutionary models with data, we find that replication origin birth and death events are mainly driven by two evolutionary pressures, the first imposes that events leading to higher double-stall probability of replication forks are penalized, while the second makes less efficient origins more prone to evolutionary loss. This analysis provides an empirically grounded predictive framework for quantitative evolutionary studies of the replication timing program.

  • Marco Mauri University of Edinburgh

    Conditions and trade-offs to enhance protein production in synthetic bacterial communities

    In nature, microorganisms occur in communities comprising a variety of mutually interacting species. In order to overcome the complexity of natural communities, a rapidly growing research field concerns the rational design and engineering of synthetic microbial consortia. Here, based on a quantitative model of a prototypical synthetic microbial consortium, we discuss the precise conditions under which a consortium outperforms individual species in the production of a recombinant protein. Moreover, we identify the inherent trade-offs between productivity and efficiency of substrate utilization.

  • Giulia Pisegna University of Rome La Sapienza

    Dynamical renormalization group approach to the collective behavior of swarms

    We study the critical behavior of a model with non-dissipative couplings aimed at describing the collective behavior of natural swarms, using the dynamical renormalization group under a fixed-network approximation. At one loop, we find a crossover between an unstable fixed point, characterized by a dynamical critical exponent z = d/2, and a stable fixed point with z = 2, a result we confirm through numerical simulations. The crossover is regulated by a length scale given by the ratio between the transport coefficient and the effective friction, so that in finite-size biological systems with low dissipation, dynamics is ruled by the unstable fixed point. In three dimensions this mechanism gives z = 3/2, a value significantly closer to the experimental window, 1.0 < z <1.3, than the value z ≃ 2 numerically found in fully dissipative models, either at or off equilibrium. This result indicates that non-dissipative dynamical couplings are necessary to develop a theory of natural swarms fully consistent with experiments.

  • Henry Mattingly MCDB Yale University

    E. coli chemotaxis is information-limited

    Organisms acquire sensory information to guide behavioral decisions. Past studies have used information theory to understand the maximum amount of information biological sensing systems can transmit, showing that in some cases they can approach the theoretical limits. However, how information constrains the ability of organisms to perform behavioral tasks remains unknown. Here we show that the information a bacterium’s sensory system acquires during navigation sets an upper limit on how fast it can climb a chemical gradient. Then, we quantify how much information E. coli cells acquire by measuring swimming statistics, signal transduction responses, and noise fluctuations in single cells. Finally, measuring their gradient-climbing speeds and comparing to the theoretical limit, we determine how efficiently E. coli use information to navigate.

17h30 - 18h00 Virtual cocktail

Organizers

Meriem Bensouda1, Victor Chardès1, Mathilde Lacroix2, María Ruiz Ortega1, Natanael Spisak1, Gabriel Thon3

1ENS Paris, 2Institut Curie, 3Université Paris-Diderot

IRN "Predictability, Adaptation, Navigation"
Laboratoire de Physique de l