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

Julieann I. Puleo, Sara S. Parker, Mackenzie R. Roman, Adam W. Watson, Kiarash Rahmani Eliato, Leilei Peng, Kathylynn Saboda, Denise J. Roe, Robert Ros, Frank B. Gertler, Ghassan Mouneimne

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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.

Original languageEnglish (US)
Pages (from-to)4215-4235
Number of pages21
JournalThe Journal of cell biology
Volume218
Issue number12
DOIs
StatePublished - Dec 2 2019

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ASJC Scopus subject areas

  • Cell Biology

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Puleo, J. I., Parker, S. S., Roman, M. R., Watson, A. W., Eliato, K. R., Peng, L., Saboda, K., Roe, D. J., Ros, R., Gertler, F. B., & Mouneimne, G. (2019). Mechanosensing during directed cell migration requires dynamic actin polymerization at focal adhesions. The Journal of cell biology, 218(12), 4215-4235. https://doi.org/10.1083/jcb.201902101