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J Cell Biol. 2019 Oct 8. pii: jcb.201902101. doi: 10.1083/jcb.201902101. [Epub ahead of print]

Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions.

Author information

1
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, AZ.
2
Department of Physics, Center for Biological Physics, and Biodesign Institute, Arizona State University, Tempe, AZ.
3
College of Optical Sciences, University of Arizona, Tucson, AZ.
4
University of Arizona Cancer Center and Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ.
5
The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA.
6
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.
7
Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, AZ gmouneimne@email.arizona.edu.

Abstract

The mechanical properties of a cell's microenvironment influence many aspects of cellular behavior, including cell migration. Durotaxis, the migration toward increasing matrix stiffness, has been implicated in processes ranging from development to cancer. During durotaxis, mechanical stimulation by matrix rigidity leads to directed migration. Studies suggest that cells sense mechanical stimuli, or mechanosense, through the acto-myosin cytoskeleton at focal adhesions (FAs); however, FA actin cytoskeletal remodeling and its role in mechanosensing are not fully understood. Here, we show that the Ena/VASP family member, Ena/VASP-like (EVL), polymerizes actin at FAs, which promotes cell-matrix adhesion and mechanosensing. Importantly, we show that EVL regulates mechanically directed motility, and that suppression of EVL expression impedes 3D durotactic invasion. We propose a model in which EVL-mediated actin polymerization at FAs promotes mechanosensing and durotaxis by maturing, and thus reinforcing, FAs. These findings establish dynamic FA actin polymerization as a central aspect of mechanosensing and identify EVL as a crucial regulator of this process.

PMID:
31594807
DOI:
10.1083/jcb.201902101

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