Collective cell guidance by cooperative intercellular forces

Abstract

Cells comprising a tissue migrate as part of a collective. How collective processes are coordinated over large multi-cellular assemblies has remained unclear, however, because mechanical stresses exerted at cell-cell junctions have not been accessible experimentally. We report here maps of these stresses within and between cells comprising a monolayer. Within the cell sheet there arise unanticipated fluctuations of mechanical stress that are severe, emerge spontaneously, and ripple across the monolayer. This stress landscape becomes increasingly rugged, sluggish, and cooperative with increasing system density. Within that landscape, local cellular migrations follow local orientations of maximal principal stress. Migrations of both endothelial and epithelial monolayers conform to this behavior, as do breast cancer cell lines before but not after the epithelial-mesenchymal transition. Collective migration in these diverse systems is seen to be governed by a simple but unifying physiological principle: neighboring cells join forces to transmit appreciable normal stress across the cell-cell junction, but migrate along orientations of minimal intercellular shear stress.

Cell Growth Rate Dictates the Onset of Glass to Fluidlike Transition and Long Time Superdiffusion in an Evolving Cell Colony

“…Dysfunctional cell birth and death control mechanisms lead to several physiological diseases, including cancers [2]. Together with genetic cues controlling birth-death processes, mechanical behavior of a collection of cells is thought to be of fundamental importance in biological processes such as embryogenesis, wound healing, stem cell dynamics, morphogenesis, tumorigenesis, and metastasis [3][4][5][6][7][8]. Because of the interplay between birth-death processes and cell-cell interactions, we expect that the collective motion of cells ought to exhibit unusual nonequilibrium dynamics, whose understanding might hold the key to describing tumor invasion and related phenomena.…”

Spatial moment dynamics for collective cell movement incorporating a neighbour-dependent directional bias

“…A desire to understand how large numbers of individuals are able to coordinate their movement has fuelled extensive studies into the interactions occurring between migrating cells [5][6][7]. Some interactions act as attractive forces to drive cells towards one another, for example, the physical coupling of neighbouring cells [8] or the release and detection of diffusible chemoattractant signals which give rise to chemotaxis [9,10]. Alternatively, movement in response to a cell-secreted chemorepellant can have a repulsive effect where cells are biased to move away from their nearest neighbours [11,12].…”

Comparative study of non-invasive force and stress inference methods in tissue

“…a e-mail: shuji@complex.c.u-tokyo.jp Measuring tissue stress is therefore useful for deepening our understanding of morphogenesis and its physical constraints. Various in vivo mechanical measurement methods have been developed; these include elastography [18], photoelasticity [19], magnetic micromanipulation [20], tonometry [21], nanoindentation [22], and monolayer stress microscopy (MSM) [23]. Among them, laser ablation of individual cell junctions is most frequently used as a tool to evaluate the tension acting on a contact surface of epithelial cells [11,24].…”