Cell-cell adhesion cannot sustain extended follower streams in a minimal non-local model of leader-follower migration

TL;DR

This study shows that a minimal non-local adhesion model cannot sustain long follower streams in collective cell migration, indicating a need for more advanced models.

Contribution

The paper demonstrates the limitations of standard non-local adhesion models in maintaining extended migratory streams, suggesting the development of extended models.

Findings

Small follower cohorts are possible but limited in size.

Adhesive interaction lengthscale constrains cohort size.

Standard models cannot reproduce in vivo extended streams.

Abstract

Cell-cell adhesion is widely hypothesised to maintain cohesion within the long streams of follower cells that trail leader subpopulations during collective migration, including in neural crest cell migration, angiogenesis, and cancer cell invasion. Mathematically, non-local advection-diffusion equations provide the canonical continuum framework within which to study such adhesive cell-cell interactions. Here, we study a minimal model of leader-follower migration within this framework, in which leaders migrate at constant velocity while followers are attracted to leaders and to one another over a finite spatial interaction range. Numerical simulations reveal that, although the model can maintain small cohorts of travelling follower cells, the size of these cohorts is limited by the adhesive interaction lengthscale, and is far below what is needed to reproduce the extended streams observed in vivo. This points to a structural limitation of the standard non-local adhesion formulation and highlights the need for the development of extended continuum models capable of sustaining long, coherent migratory streams through purely mass-conserving collective cell movement.