Shape-velocity correlation defines polarization in migrating cell simulations

Abstract

Cell migration plays essential roles in development, wound healing, diseases, and in the maintenance of a complex body. Experiments in collective cell migration generally measure quantities such as cell displacement and velocity. The observed short-time diffusion regime for mean square displacement in single-cell migration experiments on flat surfaces calls into question the definition of cell velocity and the measurement protocol. Theoretical results in stochastic modeling for single-cell migration have shown that this fast diffusive regime is explained by a white noise acting on displacement on the direction perpendicular to the migrating cell polarization axis (not on velocity). The prediction is that only the component of velocity parallel to the polarization axis is a well-defined quantity, with a robust measurement protocol. Here, we ask whether we can find a definition of a migrating-cell polarization that is able to predict the cell's subsequent displacement, based on measurements of its shape. Supported by experimental evidence that cell nucleus lags behind the cell center of mass in a migrating cell, we propose a robust parametrization for cell migration where the distance between cell nucleus and the cell's center of mass defines cell shape polarization. We tested the proposed methods by applying to a simulation model for three-dimensional cells performed in the CompuCell3D environment, previously shown to reproduce biological cells kinematics migrating on a flat surface.