Chase-and-run dynamics in cell motility and the molecular rupture of interacting active elastic dimers.

Abstract

Cell migration in morphogenesis and cancer metastasis typically involves interplay between different cell types. We construct and study a minimal, one-dimensional model composed of two different motile cells with each cell represented as an active elastic dimer. The interaction between the two cells via cadherins is modeled as a spring that can rupture beyond a threshold force as it undergoes dynamic loading from the interacting motile cells. We obtain a phase diagram consisting of chase-and-run dynamics and clumping dynamics as a function of the stiffness of the interaction spring and the threshold force and, therefore, posit that active rupture, or rupture via active forces, is a mechanosensitive means to regulate dynamics between cells. Since the parameters in the model differentiate between N- and E-cadherins, we make predictions for the interactions between a placodelike cell and a neural crestlike cell in a microchannel as well as discuss how our results inform chase-and-run dynamics found in a group of placode cells interacting with a group of neural crest cells. In particular, an argument was made in the latter case that the feedback between cadherins and cell-substrate interaction via integrins was necessary to obtain the chase-and-run behavior. Based on our two-cell results, we argue that this feedback accentuates, but is not necessary for, the chase-and-run behavior.