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

Abstract

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.

Local light-activation of the Src oncoprotein in an epithelial monolayer promotes collective extrusion

“…The tissue deformation therefore results from the interactions between these two populations. Recent studies have demonstrated the importance of mechanical forces in the competition that takes place between normal and transformed epithelial cells 37,53,54 . We showed that the traction forces are pointing outwards at the interface between the two cell populations, while the surrounding normal cells converge towards the aggregate and eventually get incorporated in it.…”

Tracking collective cell motion by topological data analysis

“…As we can see in Fig 3, the velocity field obtained from the simulations, Fig 3(b), is very similar to that measured by PIV analysis [16], Fig 3(a). For AMA, we choose a random configuration having the same number of wt and Ras cells separated by a vertical straight line and we set a known velocity distribution from experiments [27]. This represents the situation of the two monolayers when they first make contact.…”

“…Interesting dynamics occurs as an epithelial cell aggregate advances through an empty space, as in wound healing, or it collides and encroaches a different tissue, as in cancer invasion. Advancing cellular fronts may display wave phenomena [15,36], grow fingers [16,37,38], or breakdown and interpenetration against an oppositely moving front [22,27]. Different aspects of these phenomena have been studied by models ranging from macroscopic continuum mechanics to detailed subcellular agent models [25,29,37,39,40].…”

“…Here we combine particle dynamics [16] with the active vertex model (AVM) [39] to provide a cellular dynamics perspective on monolayers colliding in antagonistic migration assays (AMA) [22,27] or on monolayers spreading over an empty space [11,16,37,38]. The resulting model describes the collective migration dynamics of a large number of cells and implements exchanges of neighboring cells automatically (T1 transitions) [39].…”

“…In AMA with Human Embryonic Kidney (HEC) cell assemblies, precancerous Ras modified cells displace normal cells [27]. These latter experiments have been interpreted using continuum mechanics in a simple biophysical model through phenomenological couplings [38], without recourse to biochemical signaling mechanisms and without clear relations to cellular processes.…”