Effect of Contact Inhibition Locomotion on confined cellular organization

Abstract

Experiments performed using micro-patterned one dimensional collision assays have allowed a precise quantitative analysis of the collective manifestation of contact inhibition locomotion (CIL) wherein, individual migrating cells reorient their direction of motion when they come in contact with other cells. Inspired by these experiments, we present a discrete, minimal 1D Active spin model that mimics the CIL interaction between cells in one dimensional channels. We analyze the emergent collective behaviour of migrating cells in such confined geometries, as well as the sensitivity of the emergent patterns to driving forces that couple to cell motion. In the absence of vacancies, akin to dense cell packing, the translation dynamics is arrested and the model reduces to an equilibrium spin model which can be solved exactly. In the presence of vacancies, the interplay of activity-driven translation, cell polarity switching, and CIL results in an exponential steady cluster size distribution. We define a dimensionless Péclet number Q - the ratio of the translation rate and directional switching rate of particles in the absence of CIL. While the average cluster size increases monotonically as a function of Q, it exhibits a non-monotonic dependence on CIL strength, when the Q is sufficiently high. In the high Q limit, an analytical form of average cluster size can be obtained approximately by effectively mapping the system to an equivalent equilibrium process involving clusters of different sizes wherein the cluster size distribution is obtained by minimizing an effective Helmholtz free energy for the system. The resultant prediction of exponential dependence on CIL strength of the average cluster size and Q^{1/2} dependence of the average cluster size is borne out to reasonable accuracy as long as the CIL strength is not very large.