arXiv subjects

Philippe Marcq

Publications and source records attributed to Philippe Marcq.

At least 19 recordsLinked to original sources

arXiv2024

Src Kinase Slows Collective Rotation of Confined Epithelial Cell Monolayers

Collective cell migration is key during development, wound healing and metastasis and relies on coordinated cell behaviors at the group level. Src kinase is a key signalling protein for physiological functions of epithelia, as it regulates many cellular processes, including adhesion, motility, and mechanotransduction. Its over-activation is associated to cancer aggressiveness. Here, we take advantage of optogenetics to precisely control Src activation in time and show that its pathological-like activation slows collective rotation of epithelial cells confined into circular adhesive patches. We interpret velocity, force and stress data during period of non-activation and period of activation of Src thanks to an hydrodynamic description of the cell assembly as a polar active fluid. Src activation leads to a 2-fold decrease in the ratio of polar angle to friction, which could result from increased adhesiveness at the cell-substrate interface. Measuring internal stress allows us to show that active stresses are subdominant compared to traction forces. Our work reveals the importance of fine-tuning the level of Src activity for coordinated collective behaviors.

q-bio.TO↗

arXiv2022

Mapping cell cortex rheology to tissue rheology, and vice-versa

The mechanics of biological tissues mainly proceeds from the cell cortex rheology. A direct, explicit link between cortex rheology and tissue rheology remains lacking, yet would be instrumental in understanding how modulations of cortical mechanics may impact tissue mechanical behaviour. Using an ordered geometry built on 3D hexagonal, incompressible cells, we build a mapping relating the cortical rheology to the monolayer tissue rheology. Our approach shows that the tissue low frequency elastic modulus is proportional to the rest tension of the cortex, as expected from the physics of liquid foams as well as of tensegrity structures. A fractional visco-contractile cortex rheology is predicted to yield a high-frequency fractional visco-elastic monolayer rheology, where such a fractional behaviour has been recently observed experimentally at each scale separately. In particular cases, the mapping may be inverted, allowing to derive from a given tissue rheology the underlying cortex rheology. Interestingly, applying the same approach to a 2D hexagonal tiling fails, which suggests that the 2D character of planar cell cortex-based models may be unsuitable to account for realistic monolayer rheologies. We provide quantitative predictions, amenable to experimental tests through standard perturbation assays of cortex constituents, and hope to foster new, challenging mechanical experiments on cell monolayers.

cond-mat.soft↗

arXiv2018

Collective stresses drive competition between monolayers of normal and Ras-transformed cells

We study the competition for space between two cell lines that differ only in the expression of the Ras oncogene. The two cell populations are initially separated and set to migrate antagonistically towards an in-between stripe of free substrate. After contact, their interface moves towards the population of normal cells. We interpret the velocity and traction force data taken before and after contact thanks to a hydrodynamic description of collectively migrating cohesive cell sheets. The kinematics of cells, before and after contact, allows us to estimate the relative material parameters for both cell lines. As predicted by the model, the transformed cell population with larger collective stresses pushes the wild type cell population.

q-bio.TO↗

arXiv2017

Emergence of epithelial cell density waves

Epithelial cell monolayers exhibit traveling mechanical waves. We rationalize this observation thanks to a hydrodynamic description of the monolayer as a compressible, active and polar material. We show that propagating waves of the cell density, polarity, velocity and stress fields may be due to a Hopf bifurcation occurring above threshold values of active coupling coefficients.

physics.bio-ph↗

arXiv2017

Cell growth, division and death in cohesive tissues: a thermodynamic approach

Cell growth, division and death are defining features of biological tissues that contribute to morphogenesis. In hydrodynamic descriptions of cohesive tissues, their occurrence implies a non-zero rate of variation of cell density. We show how linear nonequilibrium thermodynamics allows to express this rate as a combination of relevant thermodynamic forces: chemical potential, velocity divergence, and activity. We illustrate the resulting effects of the non-conservation of cell density on simple examples inspired by recent experiments on cell monolayers, considering first the velocity of a spreading front, and second an instability leading to mechanical waves.

q-bio.TO↗

arXiv2017

From cells to tissue: A continuum model of epithelial mechanics

A continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model can include finite deformation, and incorporates stress and deformation tensors, which can be compared with experimental data. Using this model, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow. This study provides an integrated scheme for the understanding of the mechanisms that are involved in orchestrating the morphogenetic processes in individual cells, in order to achieve epithelial tissue morphogenesis.

q-bio.TO↗

arXiv2016

One-dimensional collective migration of a proliferating cell monolayer

The importance of collective cellular migration during embryogenesis and tissue repair asks for a sound understanding of underlying principles and mechanisms. Here, we address recent in vitro experiments on cell monolayers which show that the advancement of the leading edge relies on cell proliferation and protrusive activity at the tissue margin. Within a simple viscoelastic mechanical model amenable to detailed analysis, we identify a key parameter responsible for tissue expansion, and we determine the dependence of the monolayer velocity as a function of measurable rheological parameters. Our results allow us to discuss the effects of pharmacological perturbations on the observed tissue dynamics.

q-bio.QM↗

arXiv2015

Colloquium: Mechanical formalisms for tissue dynamics

The understanding of morphogenesis in living organisms has been renewed by tremendous progressin experimental techniques that provide access to cell-scale, quantitative information both on theshapes of cells within tissues and on the genes being expressed. This information suggests that ourunderstanding of the respective contributions of gene expression and mechanics, and of their crucialentanglement, will soon leap forward. Biomechanics increasingly benefits from models, which assistthe design and interpretation of experiments, point out the main ingredients and assumptions, andultimately lead to predictions. The newly accessible local information thus calls for a reflectionon how to select suitable classes of mechanical models. We review both mechanical ingredientssuggested by the current knowledge of tissue behaviour, and modelling methods that can helpgenerate a rheological diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and tissue scale ("inter-cell") contributions. We recall the mathematical framework developpedfor continuum materials and explain how to transform a constitutive equation into a set of partialdifferential equations amenable to numerical resolution. We show that when plastic behaviour isrelevant, the dissipation function formalism appears appropriate to generate constitutive equations;its variational nature facilitates numerical implementation, and we discuss adaptations needed in thecase of large deformations. The present article gathers theoretical methods that can readily enhancethe significance of the data to be extracted from recent or future high throughput biomechanicalexperiments.

physics.bio-ph↗

arXiv2014

Border forces and friction control epithelial closure dynamics

Epithelization, the process whereby an epithelium covers a cell-free surface, is not only central to wound healing but also pivotal in embryonic morphogenesis, regeneration, and cancer. In the context of wound healing, the epithelization mechanisms differ depending on the sizes and geometries of the wounds as well as on the cell type while a unified theoretical decription is still lacking. Here, we used a barrier-based protocol that allows for making large arrays of well-controlled circular model wounds within an epithelium at confluence, without injuring any cells. We propose a physical model that takes into account border forces, friction with the substrate, and tissue rheology. Despite the presence of a contractile actomyosin cable at the periphery of the wound, epithelization was mostly driven by border protrusive activity. Closure dynamics was quantified by an epithelization coefficient $D = σ_p/ξ$ defined as the ratio of the border protrusive stress $σ_p$ to the friction coefficient $ξ$ between epithelium and substrate. The same assay and model showed a high sensitivity to the RasV12 mutation on human epithelial cells, demonstrating the general applicability of the approach and its potential to quantitatively characterize metastatic transformations.

q-bio.CB↗

arXiv2014

Spatio-temporal dynamics of an active, polar, viscoelastic ring

Constitutive equations for a one-dimensional, active, polar, viscoelastic liquid are derived by treating the strain field as a slow hydrodynamic variable. Taking into account the couplings between strain and polarity allowed by symmetry, the hydrodynamics of an active, polar, viscoelastic body include an evolution equation for the polarity field that generalizes the damped Kuramoto-Sivashinsky equation. Beyond thresholds of the active coupling coefficients between the polarity and the stress or the strain rate, bifurcations of the homogeneous state lead first to stationary waves, then to propagating waves of the strain, stress and polarity fields. I argue that these results are relevant to living matter, and may explain rotating actomyosin rings in cells and mechanical waves in epithelial cell monolayers.

cond-mat.soft↗

arXiv2012

Contraction of cross-linked actomyosin bundles

Cross-linked actomyosin bundles retract when severed in vivo by laser ablation, or when isolated from the cell and micromanipulated in vitro in the presence of ATP. We identify the time scale for contraction as a viscoelastic time tau, where the viscosity is due to (internal) protein friction. We obtain an estimate of the order of magnitude of the contraction time tau ~ 10-100 s, consistent with available experimental data for circumferential microfilament bundles and stress fibers. Our results are supported by an exactly solvable, hydrodynamic model of a retracting bundle as a cylinder of isotropic, active matter, from which the order of magnitude of the active stress is estimated.

q-bio.QM↗

arXiv2012

Mechanical state, material properties and continuous description of an epithelial tissue

During development, epithelial tissues undergo extensive morphogenesis based on coordinated changes of cell shape and position over time. Continuum mechanics describes tissue mechanical state and shape changes in terms of strain and stress. It accounts for individual cell properties using only a few spatially averaged material parameters. To determine the mechanical state and parameters in the Drosophila pupa dorsal thorax epithelium, we sever in vivo the adherens junctions around a disk-shaped domain comprising typically hundred cells. This enables a direct measurement of the strain along different orientations at once. The amplitude and anisotropy of the strain increase during development. We also measure the stress to viscosity ratio and similarly find an increase in amplitude and anisotropy. The relaxation time is of order of ten seconds. We propose a space-time, continuous model of the relaxation. Good agreement with experimental data validates the description of the epithelial domain as a continuous, linear, visco-elastic material. We discuss the relevant time and length scales. Another material parameter, the ratio of external friction to internal viscosity, is estimated by fitting the initial velocity profile. Together, our results contribute to quantify forces and displacements, and their time evolution during morphogenesis.

q-bio.CB↗

arXiv2005

Nonlinear oscillator with parametric colored noise: some analytical results

The asymptotic behavior of a nonlinear oscillator subject to a multiplicative Ornstein-Uhlenbeck noise is investigated. When the dynamics is expressed in terms of energy-angle coordinates, it is observed that the angle is a fast variable as compared to the energy. Thus, an effective stochastic dynamics for the energy can be derived if the angular variable is averaged out. However, the standard elimination procedure, performed earlier for a Gaussian white noise, fails when the noise is colored because of correlations between the noise and the fast angular variable. We develop here a specific averaging scheme that retains these correlations. This allows us to calculate the probability distribution function (P.D.F.) of the system and to derive the behavior of physical observables in the long time limit.

cond-mat.stat-mech↗

arXiv2004

Anharmonic oscillator driven by additive Ornstein-Uhlenbeck noise

We present an analytical study of a nonlinear oscillator subject to an additive Ornstein-Uhlenbeck noise. Known results are mainly perturbative and are restricted to the large dissipation limit (obtained by neglecting the inertial term) or to a quasi-white noise (i.e., a noise with vanishingly small correlation time). Here, in contrast, we study the small dissipation case (we retain the inertial term) and consider a noise with finite correlation time. Our analysis is non perturbative and based on a recursive adiabatic elimination scheme: a reduced effective Langevin dynamics for the slow action variable is obtained after averaging out the fast angular variable. In the conservative case, we show that the physical observables grow algebraically with time and calculate the associated anomalous scaling exponents and generalized diffusion constants. In the case of small dissipation, we derive an analytic expression of the stationary Probability Distribution Function (P.D.F.) which differs from the canonical Boltzmann-Gibbs distribution. Our results are in excellent agreement with numerical simulations.

cond-mat.stat-mech↗

arXiv2004

On the stochastic pendulum with Ornstein-Uhlenbeck noise

We study a frictionless pendulum subject to multiplicative random noise. Because of destructive interference between the angular displacement of the system and the noise term, the energy fluctuations are reduced when the noise has a non-zero correlation time. We derive the long time behavior of the pendulum in the case of Ornstein-Uhlenbeck noise by a recursive adiabatic elimination procedure. An analytical expression for the asymptotic probability distribution function of the energy is obtained and the results agree with numerical simulations. Lastly, we compare our method to other approximation schemes.

cond-mat.stat-mech↗

arXiv2004

Noise-induced reentrant transition of the stochastic Duffing oscillator

We derive the exact bifurcation diagram of the Duffing oscillator with parametric noise thanks to the analytical study of the associated Lyapunov exponent. When the fixed point is unstable for the underlying deterministic dynamics, we show that the system undergoes a noise-induced reentrant transition in a given range of parameters. The fixed point is stabilised when the amplitude of the noise belongs to a well-defined interval. Noisy oscillations are found outside that range, i.e., for both weaker and stronger noise.

cond-mat.stat-mech↗

arXiv2003

Stability analysis of a noise-induced Hopf bifurcation

We study analytically and numerically the noise-induced transition between an absorbing and an oscillatory state in a Duffing oscillator subject to multiplicative, Gaussian white noise. We show in a non-perturbative manner that a stochastic bifurcation occurs when the Lyapunov exponent of the linearised system becomes positive. We deduce from a simple formula for the Lyapunov exponent the phase diagram of the stochastic Duffing oscillator. The behaviour of physical observables, such as the oscillator's mean energy, is studied both close to and far from the bifurcation.

cond-mat.stat-mech↗

arXiv2003

Effects of parametric noise on a nonlinear oscillator

We study a model of a nonlinear oscillator with a random frequency and derive the asymptotic behavior of the probability distribution function when the noise is white. In the small damping limit, we show that the physical observables grow algebraically with time before the dissipative time scale is reached, and calculate the associated anomalous diffusion exponents. In the case of colored noise, with a nonzero but arbitrarily small correlation time, the characteristic exponents are modified. We determine their values thanks to a self-consistent Ansatz.

cond-mat.stat-mech↗