RT Journal Article
SR Electronic
T1 Worrying drives cell migration in mechanically unrestrained environments
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.09.372912
DO 10.1101/2020.11.09.372912
A1 Erik S. Welf
A1 Meghan K. Driscoll
A1 Etai Sapoznik
A1 Vasanth S. Murali
A1 Andrew Weems
A1 Minna Roh-Johnson
A1 Kevin M. Dean
A1 Reto Fiolka
A1 Gaudenz Danuser
YR 2020
UL http://biorxiv.org/content/early/2020/11/09/2020.11.09.372912.abstract
AB Migratory cells employ numerous strategies to navigate the very diverse 3D microenvironments found in vivo. These strategies are subdivided into those that create space by pericellular proteolysis of extracellular matrix (ECM) proteins and those that navigate existing spaces. We find that cells can employ an alternative mechanism by digging tunnels through 3D collagen networks without extracellular proteolysis. This is accomplished by persistent polarization of large dynamic membrane blebs at the closed end of the tunnel that repeatedly agitate the collagen, a process we termed mechanical worrying. We find that this agitation promotes breakage and internalization of collagen at the cell front along with extracellular fluid in a macropinocytosis-driven manner. Membrane blebs are short-lived relative to the timescale of migration, and thus their polarization is critical for persistent ablation of the ECM. We find that sustained interactions between the collagen at the cell front and small but persistent cortical adhesions induce PI-3 Kinase (PI3K) signaling that drives polarized bleb enlargement via the Rac1 – Arp2/3 pathway. This defines a mechanism for the reinforcement of bleb expansion against load, which enables precise ablation of mechanically unrestrained environments, such as those encountered in very compliant tissue.Competing Interest StatementThe authors have declared no competing interest.