α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions

Giovanni Meacci, Haguy Wolfenson, Shuaimin Liu, Matthew R. Stachowiak, Thomas Iskratsch, Anurag Mathur, Saba Ghassemi, Nils Gauthier, Erdem Tabdanov, James Lohner, Alexander Gondarenko, Ashok C. Chander, Pere Roca-Cusachs, Ben O'Shaughnessy, James Hone, Michael P. Sheetz

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

During spreading and migration, the leading edges of cells undergo periodic protrusion--retraction cycles. The functional purpose of these cycles is unclear. Here, using submicrometer polydimethylsiloxane pillars as substrates for cell spreading, we show that periodic edge retractions coincide with peak forces produced by local contractile units (CUs) that assemble and disassemble along the cell edge to test matrix rigidity. We find that, whereas actin rearward flow produces a relatively constant force inward, the peak of local contractile forces by CUs scales with rigidity. The cytoskeletal protein α-Actinin is shared between these two force-producing systems. It initially localizes to the CUs and subsequently moves inward with the actin flow. Knockdown of α-Actinin causes aberrant rigidity sensing, loss of CUs, loss of protrusion-retraction cycles, and, surprisingly, enables the cells to proliferate on soft matrices. We present a model based on these results in which local CUs drive rigidity sensing and adhesion formation.

Original languageEnglish (US)
Pages (from-to)3471-3479
Number of pages9
JournalMolecular Biology of the Cell
Volume27
Issue number22
DOIs
StatePublished - Nov 7 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Meacci, G., Wolfenson, H., Liu, S., Stachowiak, M. R., Iskratsch, T., Mathur, A., Ghassemi, S., Gauthier, N., Tabdanov, E., Lohner, J., Gondarenko, A., Chander, A. C., Roca-Cusachs, P., O'Shaughnessy, B., Hone, J., & Sheetz, M. P. (2016). α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions. Molecular Biology of the Cell, 27(22), 3471-3479. https://doi.org/10.1091/mbc.E16-02-0107