Cortical Contractility Triggers a Stochastic Switch to Fast Amoeboid Cell Motility

Summary

3D amoeboid cell migration is central to many developmental and disease-related processes such as cancer metastasis. Here, we identify a unique prototypic amoeboid cell migration mode in early zebrafish embryos, termed stable-bleb migration. Stable-bleb cells display an invariant polarized balloon-like shape with exceptional migration speed and persistence. Progenitor cells can be reversibly transformed into stable-bleb cells irrespective of their primary fate and motile characteristics by increasing myosin II activity through biochemical or mechanical stimuli. Using a combination of theory and experiments, we show that, in stable-bleb cells, cortical contractility fluctuations trigger a stochastic switch into amoeboid motility, and a positive feedback between cortical flows and gradients in contractility maintains stable-bleb cell polarization. We further show that rearward cortical flows drive stable-bleb cell migration in various adhesive and non-adhesive environments, unraveling a highly versatile amoeboid migration phenotype.

Graphical Abstract

Highlights

• •

  Embryonic progenitor cells transform into a prototypic amoeboid migration mode

• •

  Contractility driven cortical network instabilities drive rapid cell polarization

• •

  Cell polarization is maintained by a positive cortical feedback loop

• •

  Cortical flows drive fast and persistent cell motility in confined 3D environments

Abstract

Cell-intrinsic fluctuation in cortical contraction forces triggers the switch in motility behavior that allows embryonic progenitor cells to acquire a fast and persistent migratory mode in confined 3D environments