Cortical contractility triggers a stochastic switch to fast amoeboid cell motility Ruprecht, Verena ; https://orcid.org/0000-0003-4088-8633 Wieser, Stefan ; https://orcid.org/0000-0002-2670-2217 Callan Jones, Andrew Smutny, Michael ; https://orcid.org/0000-0002-5920-9090 Morita, Hitoshi Sako, Keisuke ; https://orcid.org/0000-0002-6453-8075 Barone, Vanessa ; https://orcid.org/0000-0003-2676-3367 Ritsch Marte, Monika Sixt, Michael K ; https://orcid.org/0000-0002-6620-9179 Voituriez, Raphaël Heisenberg, Carl-Philipp J ; https://orcid.org/0000-0002-0912-4566 ddc:570 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. Cell Press 2015 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/1537 https://research-explorer.ista.ac.at/download/1537/5003 Ruprecht V, Wieser S, Callan Jones A, et al. Cortical contractility triggers a stochastic switch to fast amoeboid cell motility. <i>Cell</i>. 2015;160(4):673-685. doi:<a href="https://doi.org/10.1016/j.cell.2015.01.008">10.1016/j.cell.2015.01.008</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cell.2015.01.008 info:eu-repo/semantics/altIdentifier/wos/000349208800011 info:eu-repo/semantics/openAccess