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Pierre Ronceray

Publications and source records attributed to Pierre Ronceray.

At least 19 recordsLinked to original sources

A statistical-physics framework for translocation elastometry of deformable particles

A soft particle driven through a pore narrower than itself must deform to pass, and how quickly it does so is set by how hard it is to squeeze. We propose a mathematical framework for turning rate measurements of this driven, stochastic passage into quantitative mechanical measurements. Treating the entry of the particle as one-dimensional Brownian dynamics across an elastic barrier, we solve the transport problem exactly and identify two dynamical regimes: at low drive the passage is thermally activated and limited by the energy needed to deform the particle, and at high drive it is friction-limited. We propose a framework to extract the particle's deformation energy and relevant geometrical information by combining measurements in these two regimes. This method could be used in the context of nanopore sensing, where the drive is an applied voltage: the framework then provides a self-calibrating route---translocation elastometry---from a current-voltage measurement to the elasticity and shape of individual soft nanoparticles.

cond-mat.soft

Learning general pair interactions between self-propelled particles

Synthetic active matter systems, such as active colloids, often have complex interactions, which can be of hydrodynamic, chemical or electrostatic origin and cannot be computed from first principles. Here, we use Stochastic Force Inference to learn general pair interactions, including transverse forces and torques, between self-propelled Janus particles from experimental trajectories. We use data from two experiments: one where the particles flock, and one where the system remains disordered. The learned interactions are then fed to numerical simulations, which reproduce all the experimental observables and could be extrapolated to different densities. Overall, we find that the radial interaction is mostly repulsive and isotropic, while the angular interaction has a richer angular dependence, which controls the behavior of the system; the transverse interaction is negligible. Finally, testing the symmetry relations obeyed by the inferred interactions allows us to show that they cannot come from electrostatics only, so that they must have a hydrodynamic component.

cond-mat.soft

Topological defect engineering enables size and shape control in self-assembly

The self-assembly of complex structures from engineered subunits is a major goal of nanotechnology, but controlling their size becomes increasingly difficult in larger assemblies. Existing strategies present significant challenges, among which the use of multiple subunit types or the precise control of their shape and mechanics. Here we introduce an alternative approach based on identical subunits whose interactions promote crystals, but also favor crystalline defects. We theoretically show that topological restrictions on the scope of these defects in large assemblies imply that the assembly size is controlled by the magnitude of the defect-inducing interaction. Using DNA origami, we experimentally demonstrate both size and shape control in two-dimensional disk- and fiber-like assemblies. Our basic concept of defect engineering could be generalized well beyond these simple examples, and thus provide a broadly applicable scheme to control self-assembly.

cond-mat.soft

Principled model selection for stochastic dynamics

Complex dynamical systems, from macromolecules to ecosystems, are often modeled by stochastic differential equations. To learn such models from data, a common approach involves sparse selection among a large function library. However, we show that overfitting arises not just from individual model complexity, but also from the combinatorial growth of possible models. To address this, we introduce Parsimonious Stochastic Inference (PASTIS), a principled method combining likelihood-estimation statistics with extreme value theory to suppress superfluous parameters. PASTIS outperforms existing methods and reliably identifies minimal models, even with low sampling rates or measurement error. It extends to stochastic partial differential equations, and applies to ecological networks and reaction-diffusion dynamics.

cond-mat.soft

Learning dynamical models from stochastic trajectories

The dynamics of biological systems, from proteins to cells to organisms, is complex and stochastic. To decipher their physical laws, we need to bridge between experimental observations and theoretical modeling. Thanks to progress in microscopy and tracking, there is today an abundance of experimental trajectories reflecting these dynamical laws. Inferring physical models from noisy and imperfect experimental data, however, is challenging. Because there are no inference methods that are robust and efficient, model reconstruction from experimental trajectories is a bottleneck to data-driven biophysics. In this Thesis, I present a set of tools developed to bridge this gap and permit robust and universal inference of stochastic dynamical models from experimental trajectories. These methods are rooted in an information-theoretical framework that quantifies how much can be inferred from trajectories that are short, partial and noisy. They permit the efficient inference of dynamical models for overdamped and underdamped Langevin systems, as well as the inference of entropy production rates. I finally present early applications of these techniques, as well as future research directions.

cond-mat.soft

Inferring geometrical dynamics of cell nucleus translocation

The ability of eukaryotic cells to squeeze through constrictions is limited by the stiffness of their large and rigid nucleus. However, migrating cells are often able to overcome this limitation and pass through constrictions much smaller than their nucleus, a mechanism that is not yet understood. This is what we address here through a data-driven approach using microfluidic devices where cells migrate through controlled narrow spaces of sizes comparable to the ones encountered in physiological situations. Stochastic Force Inference is applied to experimental nuclear trajectories and nuclear shape descriptors, resulting in equations that effectively describe this phenomenon of nuclear translocation. By employing a model where the channel geometry is an explicit parameter and by training it over experimental data with different sizes of constrictions, we ensure that the resulting equations are predictive to other geometries. Altogether, the approach developed here paves the way for a mechanistic and quantitative description of dynamical cell complexity during its motility.

physics.bio-ph

How do particles with complex interactions self-assemble?

In living cells, proteins self-assemble into large functional structures based on specific interactions between molecularly complex patches. Due to this complexity, protein self-assembly results from a competition between a large number of distinct interaction energies, of the order of one per pair of patches. Current self-assembly models however typically ignore this aspect, and the principles by which it determines the large-scale structure of protein assemblies are largely unknown. Here, we use Monte-Carlo simulations and machine learning to start to unravel these principles. We observe that despite widespread geometrical frustration, aggregates of particles with complex interactions fall within only a few categories that often display high degrees of spatial order, including crystals, fibers, and oligomers. We then successfully identify the most relevant aspect of the interaction complexity in predicting these outcomes, namely the particles' ability to form periodic structures. Our results provide a first extensive characterization of the rich design space associated with identical particles with complex interactions, and could inspire engineered self-assembling nanoobjects as well as help understand the emergence of robust functional protein structures.

cond-mat.soft

Nonlinear mechanosensation in fiber networks

In a diversity of physiological contexts, eukaryotic cells adhere to an extracellular matrix (ECM), a disordered network with complex nonlinear mechanics. Such cells can perform mechanosensation: using local force probing they can measure and respond to their substrate's mechanical properties. It remains unclear, however, how the mechanical complexity of the ECM at the cellular scale impacts mechanosensation. Here, we investigate the physical limits of mechanosensation imposed by the inherent structural disorder and nonlinear elastic response of the ECM. Using a theoretical framework for disordered fiber networks, we find that the extreme mechanical heterogeneity that cells can locally sense with small probing forces is strongly reduced with increasing force. Specifically, we predict that the accuracy of mechanosensation dramatically improves with force, following a universal power law insensitive to constitutive details, which we quantitatively confirm using microrheology experiments in collagen and fibrin gels. We provide conceptual insights into this behavior by introducing a general model for nonlinear mechanosensation, based on the idea of an emergent nonlinear length-scale associated with fiber buckling. This force-dependent length-scale enhances the range over which local mechanical measurements are performed, thereby averaging the response of a disordered network over an enlarged region. We show with an example how a cell can use this nonlinear mechanosensation to infer the macroscopic mechanical properties of a disordered ECM using local measurements. Together, our results demonstrate that cells can take advantage of the inherent nonlinearity of fibrous networks to robustly sense, control, and respond to their mechanical environment.

cond-mat.soft

Local Nonlinear Elastic Response of Extracellular Matrices

Nonlinear stiffening is a ubiquitous property of major types of biopolymers that make up the extracellular matrices (ECM) including collagen, fibrin and basement membrane. Within the ECM, many types of cells such as fibroblasts and cancer cells are known to mechanically stretch their surroundings that locally stiffens the matrix. Although the bulk nonlinear elastic behaviors of these biopolymer networks are well studied, their local mechanical responses remain poorly characterized. Here, to understand how a living cell feels the nonlinear mechanical resistance from the ECM, we mimic the cell-applied local force using optical tweezers; we report that the local stiffening responses in highly nonlinear ECM are significantly weaker than responses found in bulk rheology, across two orders of magnitude of the locally applied force since the onset of stiffening. With a minimal model, we show that a local point force application can induce a stiffened region in the matrix, which expands with increasing magnitude of the point force. Furthermore, we show that this stiffened region behaves as an effective probe upon local loading. The local nonlinear elastic response can be attributed to the nonlinear growth of this effective probe that linearly deforms an increasing portion of the matrix.

cond-mat.soft

Self-organization and shape change by active polarization in nematic droplets

Active forces occurring within cells can drive crucial biological processes that involve spontaneous organization and shape change, such as cell division. Motivated by recent in vitro experiments of nematic droplets of cytoskeletal filaments and motors that self-organize and divide, we present a minimal hydrodynamic model that combines the nonequilibrium kinetics of motor-filament interactions with equilibrium nematic phase separation. The motors organize within droplets and structure filaments into polarized aster defects. At large motor activity, they can even deform or divide the droplet, or form multi-aster chains of droplets. Our predicted phase diagram recapitulates these experimentally observed shapes.

cond-mat.soft

Liquid demixing in elastic networks: cavitation, permeation, or size selection?

Demixing of multicomponent biomolecular systems via liquid-liquid phase separation (LLPS) has emerged as a potentially unifying mechanism governing the formation of several membrane-less intracellular organelles ("condensates"), both in the cytoplasm (e.g., stress granules) and in the nucleoplasm (e.g., nucleoli). While both in vivo experiments and studies of synthetic systems demonstrate that LLPS is strongly affected by the presence of a macromolecular elastic network, a fundamental understanding of the role of such networks on LLPS is still lacking. Here we show that, upon accounting for capillary forces responsible for network expulsion, small-scale heterogeneity of the network, and its nonlinear mechanical properties, an intriguing picture of LLPS emerges. Specifically, we predict that, in addition to the experimentally observed cavitated droplets which fully exclude the network, two other phases are thermodynamically possible: elastically arrested, size-limited droplets at the network pore scale, and network-including macroscopic droplets. In particular, pore size-limited droplets may emerge in chromatin networks, with implications for structure and function of nucleoplasmic condensates.

cond-mat.soft

Stoichiometry controls the dynamics of liquid condensates of associative proteins

Multivalent associative proteins with strong complementary interactions play a crucial role in phase separation of intracellular liquid condensates. We study the internal dynamics of such "bond-network" condensates comprised of two complementary proteins via scaling analysis and molecular dynamics. We find that when stoichiometry is balanced, relaxation slows down dramatically due to a scarcity of alternative partners following a bond break. This microscopic slow-down strongly affects the bulk diffusivity, viscosity and mixing, which provides a means to experimentally test our predictions.

cond-mat.soft

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

The migratory dynamics of cells in physiological processes, ranging from wound healing to cancer metastasis, rely on contact-mediated cell-cell interactions. These interactions play a key role in shaping the stochastic trajectories of migrating cells. While data-driven physical formalisms for the stochastic migration dynamics of single cells have been developed, such a framework for the behavioral dynamics of interacting cells still remains elusive. Here, we monitor stochastic cell trajectories in a minimal experimental 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 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 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.

physics.bio-ph

Inferring the dynamics of underdamped stochastic systems

Many complex systems, ranging from migrating cells to animal groups, exhibit stochastic dynamics described by the underdamped Langevin equation. Inferring such an equation of motion from experimental data can provide profound insight into the physical laws governing the system. Here, we derive a principled framework to infer the dynamics of underdamped stochastic systems from realistic experimental trajectories, sampled at discrete times and subject to measurement errors. This framework yields an operational method, Underdamped Langevin Inference (ULI), which performs well on experimental trajectories of single migrating cells and in complex high-dimensional systems, including flocks with Viscek-like alignment interactions. Our method is robust to experimental measurement errors, and includes a self-consistent estimate of the inference error.

physics.bio-ph

Learning force fields from stochastic trajectories

When monitoring the dynamics of stochastic systems, such as interacting particles agitated by thermal noise, disentangling deterministic forces from Brownian motion is challenging. Indeed, we show that there is an information-theoretic bound, the capacity of the system when viewed as a communication channel, that limits the rate at which information about the force field can be extracted from a Brownian trajectory. This capacity provides an upper bound to the system's entropy production rate, and quantifies the rate at which the trajectory becomes distinguishable from pure Brownian motion. We propose a practical and principled method, Stochastic Force Inference, that uses this information to approximate force fields and spatially variable diffusion coefficients. It is data efficient, including in high dimensions, robust to experimental noise, and provides a self-consistent estimate of the inference error. In addition to forces, this technique readily permits the evaluation of out-of-equilibrium currents and the corresponding entropy production with a limited amount of data.

cond-mat.soft

Magic numbers in polymer phase separation -- the importance of being rigid

Cells possess non-membrane-bound bodies, many of which are now understood as phase-separated condensates. One class of such condensates is composed of two polymer species, where each consists of repeated binding sites that interact in a one-to-one fashion with the binding sites of the other polymer. Previous biologically-motivated modeling of such a two-component system surprisingly revealed that phase separation is suppressed for certain combinations of numbers of binding sites. This phenomenon, dubbed the "magic-number effect", occurs if the two polymers can form fully-bonded small oligomers by virtue of the number of binding sites in one polymer being an integer multiple of the number of binding sites of the other. Here we use lattice-model simulations and analytical calculations to show that this magic-number effect can be greatly enhanced if one of the polymer species has a rigid shape that allows for multiple distinct bonding conformations. Moreover, if one species is rigid, the effect is robust over a much greater range of relative concentrations of the two species. Our findings advance our understanding of the fundamental physics of two-component polymer-based phase-separation and suggest implications for biological and synthetic systems.

physics.bio-ph

The range of geometrical frustration in lattice spin models

The concept of geometrical frustration in condensed matter physics refers to the fact that a system has a locally preferred structure with an energy density lower than the infinite ground state. This notion is however often used in a qualitative sense only. In this article, we discuss a quantitative definition of geometrical frustration in the context of lattice models of binary spins. To this aim, we introduce the framework of local energy landscapes, within which frustration can be quantified as the discrepancy between the energy of locally preferred structures and the ground state. Our definition is scale-dependent and involves an optimization over a gauge class of equivalent local energy landscapes, related to one another by local energy displacements. This ensures that frustration depends only on the physical Hamiltonian and its range, and not on unphysical choices in how it is written. Our framework shows that a number of popular frustrated models, including the antiferromagnetic Ising model on a triangular lattice, only have finite-range frustration: geometrical incompatibilities are local and can be eliminated by an exact coarse-graining of the local energies.

cond-mat.stat-mech

Fiber plucking by molecular motors yields large emergent contractility in stiff biopolymer networks

The mechanical properties of the cell depend crucially on the tension of its cytoskeleton, a biopolymer network that is put under stress by active motor proteins. While the fibrous nature of the network is known to strongly affect the transmission of these forces to the cellular scale, our understanding of this process remains incomplete. Here we investigate the transmission of forces through the network at the individual filament level, and show that active forces can be geometrically amplified as a transverse motor-generated force force "plucks" the fiber and induces a nonlinear tension. In stiff and densely connnected networks, this tension results in large network-wide tensile stresses that far exceed the expectation drawn from a linear elastic theory. This amplification mechanism competes with a recently characterized network-level amplification due to fiber buckling, suggesting that that fiber networks provide several distinct pathways for living systems to amplify their molecular forces.

cond-mat.soft