Mechanics of motility initiation and motility arrest in crawling cells

Motility initiation in crawling cells requires transformation of a symmetric state into a polarized state. In contrast, motility arrest is associated with re-symmetrization of the internal configuration of a cell. Experiments on keratocytes suggest that polarization is triggered by the increased contractility of motor proteins but the conditions of re-symmetrization remain unknown. In this paper we show that if adhesion with the extra-cellular substrate is sufficiently low, the progressive intensification of motor-induced contraction may be responsible for both transitions: from static (symmetric) to motile (polarized) at a lower contractility threshold and from motile (polarized) back to static (symmetric) at a higher contractility threshold. Our model of lamellipodial cell motility is based on a 1D projection of the complex intra-cellular dynamics on the direction of locomotion. In the interest of analytical transparency we also neglect active protrusion and view adhesion as passive. Despite the unavoidable oversimplifications associated with these assumptions, the model reproduces quantitatively the motility initiation pattern in fish keratocytes and reveals a crucial role played in cell motility by the nonlocal feedback between the mechanics and the transport of active agents. A prediction of the model that a crawling cell can stop and re-symmetrize when contractility increases sufficiently far beyond the motility initiation threshold still awaits experimental verification

Initiation of motility on a compliant substrate

The conditions under which biological cells switch from a static to a motile state are fundamental to the understanding of many healthy and pathological processes. In this paper, we show that even in the presence of a fully symmetric protrusive activity at the cell edges, such a spontaneous transition can result solely from the mechanical interaction of the cell traction forces with an elastic substrate. The loss of symmetry of the traction forces leading to the cell propulsion is rooted in the fact that the surface loading follows the substrate deformation. The bifurcation between the static and motile states is characterized analytically and, considering the measurements performed on two cell types, we show that such an instability can realistically occur on soft in vivo substrates

On the quasi-static effective behaviour of poroelastic media containing elastic inclusions

The aim of the present study is to derive the effective quasi-static behaviour of a composite medium, made of a poroelastic matrix containing elastic impervious inclusions. For this purpose, the asymptotic homogenisation method is used. On the local scale, the governing equations include Biot's model of poroelasticity in the porous matrix and Navier equations in the inclusions, with elastic properties of the same order of magnitude. Biot's diphasic model of poroelasticity is obtained on the macroscopic scale, but with effective parameters that are strongly impacted by the distribution of inclusions, even at low volume fraction. The impact on fluid flow is strictly geometrical, showing that the inclusions do not play the role of a porous network

Theory of mechanochemical patterning in biphasic biological tissues.

The formation of self-organized patterns is key to the morphogenesis of multicellular organisms, although a comprehensive theory of biological pattern formation is still lacking. Here, we propose a minimal model combining tissue mechanics with morphogen turnover and transport to explore routes to patterning. Our active description couples morphogen reaction and diffusion, which impact cell differentiation and tissue mechanics, to a two-phase poroelastic rheology, where one tissue phase consists of a poroelastic cell network and the other one of a permeating extracellular fluid, which provides a feedback by actively transporting morphogens. While this model encompasses previous theories approximating tissues to inert monophasic media, such as Turing's reaction-diffusion model, it overcomes some of their key limitations permitting pattern formation via any two-species biochemical kinetics due to mechanically induced cross-diffusion flows. Moreover, we describe a qualitatively different advection-driven Keller-Segel instability which allows for the formation of patterns with a single morphogen and whose fundamental mode pattern robustly scales with tissue size. We discuss the potential relevance of these findings for tissue morphogenesis

Crawling in a fluid

There is increasing evidence that mammalian cells not only crawl on substrates but can also swim in fluids. To elucidate the mechanisms of the onset of motility of cells in suspension, a model which couples actin and myosin kinetics to fluid flow is proposed and solved for a spherical shape. The swimming speed is extracted in terms of key parameters. We analytically find super- and subcritical bifurcations from a non-motile to a motile state and also spontaneous polarity oscillations that arise from a Hopf bifurcation. Relaxing the spherical assumption, the obtained shapes show appealing trends

Mechanical behavior of multi-cellular spheroids under osmotic compression

The internal and external mechanical environment plays an important role in tumorogenesis. As a proxy of an avascular early state tumor, we use multicellular spheroids, a composite material made of cells, extracellular matrix and permeating fluid. We characterize its effective rheology at the timescale of minutes to hours by compressing the aggregates with osmotic shocks and modeling the experimental results with an active poroelastic material that reproduces the stress and strain distributions in the aggregate. The model also predicts how the emergent bulk modulus of the aggregate as well as the hydraulic diffusion of the percolating interstitial fluid are modified by the preexisting active stress within the aggregate. We further show that the value of these two phenomenological parameters can be rationalized by considering that, in our experimental context, the cells are effectively impermeable and incompressible inclusions nested in a compressible and permeable matrix