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Vinculin is required for cell polarization, migration, and extracellular matrix remodeling in 3D collagen
Author(s) -
Thievessen Ingo,
Fakhri Nikta,
Steinwachs Julian,
Kraus Viola,
McIsaac R. Scott,
Gao Liang,
Chen BiChang,
Baird Michelle A.,
Davidson Michael W.,
Betzig Eric,
Oldenbourg Rudolf,
Waterman Clare M.,
Fabry Ben
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-268235
Subject(s) - vinculin , extracellular matrix , microbiology and biotechnology , cell migration , focal adhesion , integrin , chemistry , cell adhesion , actin cytoskeleton , actin , cytoskeleton , fibronectin , cell , biology , phosphorylation , biochemistry
ABSTRACT Vinculin is filamentous (F)‐actin‐binding protein enriched in integrin‐based adhesions to the extracellular matrix (ECM). Whereas studies in 2‐dimensional (2D) tissue culture models have suggested that vinculin negatively regulates cell migration by promoting cytoskeleton‐ECM coupling to strengthen and stabilize adhesions, its role in regulating cell migration in more physiologic, 3‐dimensional (3D) environments is unclear. To address the role of vinculin in 3D cell migration, we analyzed the morphodynamics, migration, and ECM remodeling of primary murine embryonic fibroblasts (MEFs) with cre/loxP‐mediated vinculin gene disruption in 3D collagen I cultures. We found that vinculin promoted 3D cell migration by increasing directional persistence. Vinculin was necessary for persistent cell protrusion, cell elongation, and stable cell orientation in 3D collagen, but was dispensable for lamellipodia formation, suggesting that vinculin‐mediated cell adhesion to the ECM is needed to convert actin‐based cell protrusion into persistent cell shape change and migration. Consistent with this finding, vinculin was necessary for efficient traction force generation in 3D collagen without affecting myosin II activity and promoted 3D collagen fiber alignment and macroscopical gel contraction. Our results suggest that vinculin promotes directionally persistent cell migration and tension‐dependent ECM remodeling in complex 3D environments by increasing cell‐ECM adhesion and traction force generation.—Thievessen, I., Fakhri, N., Steinwachs, J., Kraus, V., McIsaac, R. S., Gao, L., Chen, B.‐C., Baird, M. A., Davidson, M. W., Betzig, E., Oldenbourg, R., Waterman, C., M., Fabry, B. Vinculin is required for cell polarization, migration, and extracellular matrix remodeling in 3D collagen. FASEB J. 29, 4555‐4567 (2015). www.fasebj.org