Coherent Motion of Monolayer Sheets under Confinement and Its Pathological Implications

Abstract

Coherent angular rotation of epithelial cells is thought to contribute to many vital physiological processes including tissue morphogenesis and glandular formation. However, factors regulating this motion, and the implications of this motion if perturbed, remain incompletely understood. In the current study, we address these questions using a cell-center based model in which cells are polarized, motile, and interact with the neighboring cells via harmonic forces. We demonstrate that, a simple evolution rule in which the polarization of any cell tends to orient with its velocity vector can induce coherent motion in geometrically confined environments. In addition to recapitulating coherent rotational motion observed in experiments, our results also show the presence of radial movements and tissue behavior that can vary between solid-like and fluid-like. We show that the pattern of coherent motion is dictated by the combination of different physical parameters including number density, cell motility, system size, bulk cell stiffness and stiffness of cell-cell adhesions. We further observe that perturbations in the form of cell division can induce a reversal in the direction of motion when cell division occurs synchronously. Moreover, when the confinement is removed, we see that the existing coherent motion leads to cell scattering, with bulk cell stiffness and stiffness of cell-cell contacts dictating the invasion pattern. In summary, our study provides an in-depth understanding of the origin of coherent rotation in confined tissues, and extracts useful insights into the influence of various physical parameters on the pattern of such movements.

Pulsations and flows in tissues: two collective dynamics with simple cellular rules

“…(i) to align with the directionv α of its instantaneous velocity and (ii) to undergo rotational diffusion, which mathematically translates to the following differential equation [32,33] dp…”

Physical models of collective cell motility: from cell to tissue

“…Interestingly, this consequence of displacement alignment is also implied by models generated by detailed tracking of human keratinocytes [36], as [42] notes. More recent papers have applied both velocity alignment and displacement alignment [70, 117, 66, 118, 119]. A related model of “mechanotaxis” has been used by [67], in which cells polarize in the direction of the time-averaged net force exerted on them.…”

Motility-Driven Glass and Jamming Transitions in Biological Tissues

“…Building on these successes, researchers have recently used self-propelled particle (SPP) models to describe dense biological tissues [4, 15, 20, 45, 48, 51]. These models are similar to those for inert particulate matter – cells are represented as disks or spheres that interact with an isotropic soft repulsive potential – but unlike Brownian particles in a thermal bath, self-propelled particles exhibit persistent random walks.…”