Modeling and analysis of collective cell migration in an in vivo three-dimensional environment

Abstract

A long-standing question in collective cell migration has been what might be the relative advantage of forming a cluster over migrating individually. Does an increase in the size of a collectively migrating group of cells enable them to sample the chemical gradient over a greater distance because the difference between front and rear of a cluster would be greater than for single cells? We combined theoretical modeling with experiments to study collective migration of the border cells in-between nurse cells in the Drosophila egg chamber. We discovered that cluster size is positively correlated with migration speed, up to a particular point above which speed plummets. This may be due to the effect of viscous drag from surrounding nurse cells together with confinement of all of the cells within a stiff extracellular matrix. The model predicts no relationship between cluster size and velocity for cells moving on a flat surface, in contrast to movement within a 3D environment. Our analyses also suggest that the overall chemoattractant profile in the egg chamber is likely to be exponential, with the highest concentration in the oocyte. These findings provide insights into collective chemotaxis by combining theoretical modeling with experimentation.cell migration | theoretical modeling | three-dimensional | chemotaxis

Physical models of collective cell motility: from cell to tissue

“…Some of these elements have been integrated into single-cell models including modeling of the flow of the actin cytoskeleton [29, 211, 226, 227] or application of minimal active fluid models [228], but the impact on collective migration is not yet clear. However, given the clear role of cytosolic hydrodynamics in development [229] and the recent suggestion that some collective cell motility may be limited by hydrodynamic flow in the surrounding tissue [230], extension of models to greater mechanical detail would be highly relevant. An initial step in this direction was recently published by Marth and Voigt, who used collective phase field models to extend a minimal active fluid cell model to handle multiple hydrodynamically-interacting cells [131].…”

Modeling collective cell migration in geometric confinement

“…Collective migration of cells occurs during the normal developmental processes [1][2][3][4], physiological responses during wound healing or in an immune response [5,6]. It also plays an important role during pathologies such as cancer metastasis [7].…”

Centering based on active diffusion in mouse oocytes is non-specific

“…S5). This suggests that friction forces scale much faster than linearly with particle size, as has been observed in Drosophila embryos 22 , and in contrast to the behavior expected in the low-Reynolds Stokes regime.…”