RT Journal Article
SR Electronic
T1 Mechanical worrying drives cell migration in crowded 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 Juan Manuel Garcia-Arcos
A1 Minna Roh-Johnson
A1 Kevin M. Dean
A1 Matthieu Piel
A1 Reto Fiolka
A1 Gaudenz Danuser
YR 2021
UL http://biorxiv.org/content/early/2021/08/12/2020.11.09.372912.abstract
AB Migratory cells navigate through crowded 3D microenvironments in vivo. Amoeboid cells, such as immune cells and some cancer cells, are thought to do so by deforming their bodies to squeeze through tight spaces.1 Yet large populations of nearly spherical amoeboid cells migrate2–4 in microenvironments too dense5,6 to move through without extensive shape deformations. How they do so is unknown. We used high-resolution light-sheet microscopy to visualize metastatic melanoma cells in dense environments, finding that cells maintain a round morphology as they migrate and create a path through which to move via bleb-driven mechanical degradation and subsequent macropinocytosis of extracellular matrix components. Proteolytic degradation of the extracellular matrix via matrix metalloproteinases is not required. Membrane blebs are short-lived relative to the timescale of migration, and thus persistence in their polarization is critical for productive ablation of the extracellular matrix. Interactions between small but long-lived cortical adhesions and collagen at the cell front induce PI-3 Kinase signaling that drive bleb enlargement via branched actin polymerization. Large blebs in turn abrade collagen, creating a feedback between extracellular matrix structure, cell morphology, and cell polarization that results in both path generation and persistent cell movement.Competing Interest StatementThe authors have declared no competing interest.