Extent of Cell Confinement in Microtracks Affects Speed and Results in Differential Matrix Strains.
Journal Article (Journal Article)
During metastasis, cancer cells navigate through a spatially heterogeneous extracellular matrix (ECM). Physical properties of ECM, including the degree of confinement, influence cell migration behavior. Here, utilizing in vitro three-dimensional collagen microtracks, we demonstrate that cell-ECM interactions, specifically the degree of spatial confinement, regulate migratory behavior. We found that cells migrate faster when they are fully confined, contacting all four walls (top, bottom, and two sides) of a collagen microtrack, compared with cells that are partially confined, contacting less than four walls. When fully confined, cells exhibit fewer but larger vinculin-containing adhesions and create greater strains in the surrounding matrix directed toward the cell body. In contrast, partially confined cells develop a more elongated morphology with smaller but significantly more vinculin-containing adhesions and displace the surrounding matrix less than fully confined cells. The resulting effect of increasing cell contractility via Rho activation is dependent on the number of walls with which the cell is in contact. Although matrix strains increase in both fully and partially confined cells, cells that are partially confined increase speed, whereas those in full confinement decrease speed. Together, these results suggest that the degree of cell-ECM contact during confined migration is a key determinant of speed, morphology, and cell-generated substrate strains during motility, and these factors may work in tandem to facilitate metastatic cell migration.
Full Text
Duke Authors
Cited Authors
- Mosier, JA; Rahman-Zaman, A; Zanotelli, MR; VanderBurgh, JA; Bordeleau, F; Hoffman, BD; Reinhart-King, CA
Published Date
- November 2019
Published In
Volume / Issue
- 117 / 9
Start / End Page
- 1692 - 1701
PubMed ID
- 31623884
Pubmed Central ID
- PMC6838744
Electronic International Standard Serial Number (EISSN)
- 1542-0086
International Standard Serial Number (ISSN)
- 0006-3495
Digital Object Identifier (DOI)
- 10.1016/j.bpj.2019.09.024
Language
- eng