Cortical Contractility Triggers a Stochastic Switch to Fast Amoeboid Cell Motility

Verena Ruprecht,Stefan Wieser,Andrew Callan-Jones,Michael Smutny,Hitoshi Morita,Keisuke Sako,Vanessa Barone,Monika Ritsch-Marte,Michael Sixt,Raphaël Voituriez,Carl-Philipp Heisenberg

doi:10.1016/j.cell.2015.01.008

Abstract

Summary3D 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.

Highlights

We have studied different migration phenotypes during zebrafish gastrulation and identified a cortical contractility-mediated cell-intrinsic motility switch to fast amoeboid migration in 3D environments, which we termed stable-bleb migratio
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
Migrating cells show a versatile repertoire of migration modes with remarkable plasticity, allowing them to switch between different migration strategies in response to changing environmental conditions and activation of distinct molecular pathways (Friedl and Alexander, 2011)

Summary

Introduction

We have studied different migration phenotypes during zebrafish gastrulation and identified a cortical contractility-mediated cell-intrinsic motility switch to fast amoeboid migration in 3D environments, which we termed stable-bleb migratio. When adding serum to the culture medium, we observed unexpected changes in progenitor cell architecture with cells displaying a highly polarized cell morphology characterized by a stable pear-like shape and a large spherical protrusion front (Figure 1C).

Results

Conclusion