Semblance of Heterogeneity in Collective Cell Migration

Cell population heterogeneity is increasingly a focus of inquiry in biological research. For example, cell migration studies have investigated the heterogeneity of invasiveness and taxis in development, wound healing, and cancer. However, relatively little effort has been devoted to exploring when heterogeneity is mechanistically relevant and how to reliably measure it. Statistical methods from the animal movement literature offer the potential to analyze heterogeneity in collections of cell tracking data. A popular measure of heterogeneity, which we use here as an example, is the distribution of delays in directional cross-correlation. Employing a suitably generic, yet minimal, model of collective cell movement in three dimensions, we show how using such measures to quantify heterogeneity in tracking data can result in the inference of heterogeneity where there is none. Our study highlights a potential pitfall in the statistical analysis of cell population heterogeneity, and we argue that this can be mitigated by the appropriate choice of null models.