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

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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

Original languageEnglish
Pages (from-to)3471-3479
Number of pages9
JournalMolecular biology of the cell
Issue number22
Accepted/In press20 Apr 2016
Published7 Nov 2016


King's Authors


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.

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