Cellular Contraction and Polarization Drive Collective Cellular Motion

Abstract

Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity.

Collective migration and cell jamming in asthma, cancer and development

“…But just as dynamical heterogeneity can emerge from a system comprising identical inert constituents, so too dynamical heterogeneity can emerge in the living confluent epithelial layer Tambe et al, 2011;Trepat et al, 2009). Within the living cell layer, however, there exists, in addition, the innate biological heterogeneities associated with cell-to-cell variations in cell type, phenotype, size, adhesion, active propulsion, polarization and cell signaling (Garcia et al, 2015;Notbohm et al, 2016;Wilk et al, 2014). These two different sources of heterogeneity -dynamical heterogeneity and cell-to-cell biological heterogeneity -are distinct but are likely to be interactive and interdependent, thereby provoking the following unanswered questions.…”

Emergence of epithelial cell density waves

“…A significant difference with the treatments proposed in [11,22] is that we take into account the compressibility of the monolayer [24,25] through the cell density balance equation (see [23] for an alternative way to treat incompressibility). Our formulation is more parsimonious than [11,22] since we do not need to introduce an evolution equation for an additional chemical field in order to generate the instability.…”

“…Since relevant experiments were performed in a quasione-dimensional geometry [8,9,11], we focus on the one dimensional case. We enforce periodic boundary conditions in a system of constant spatial extension L, with space coordinate x and time t.…”

“…The external force is assumed to be due both to fluid friction, with a friction coefficient ξ, and to active motility forces oriented along the polarity p(x, t), with an amplitude t a [10,11,22,23]:…”

Collective motion of bacteria and their dynamic assembly behavior

“…Traditionally, the active matter system can be divided into many different categories: living cells [10], microtubule system consisting of actin and myosin [11], undomesticated bacterial system [12], self-oscillated polymer gels [13], synthetic Janus particles [14][15][16][17] such as Au-Pt rods and many other types [18][19][20][21][22] (Fig. 2).…”