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

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 p...

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Autores principales: Meacci, Giovanni, Wolfenson, Haguy, Liu, Shuaimin, Stachowiak, Matthew R., Iskratsch, Thomas, Mathur, Anurag, Ghassemi, Saba, Gauthier, Nils, Tabdanov, Erdem, Lohner, James, Gondarenko, Alexander, Chander, Ashok C., Roca-Cusachs, Pere, O’Shaughnessy, Ben, Hone, James, Sheetz, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221581/
https://www.ncbi.nlm.nih.gov/pubmed/27122603
http://dx.doi.org/10.1091/mbc.E16-02-0107
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author Meacci, Giovanni
Wolfenson, Haguy
Liu, Shuaimin
Stachowiak, Matthew R.
Iskratsch, Thomas
Mathur, Anurag
Ghassemi, Saba
Gauthier, Nils
Tabdanov, Erdem
Lohner, James
Gondarenko, Alexander
Chander, Ashok C.
Roca-Cusachs, Pere
O’Shaughnessy, Ben
Hone, James
Sheetz, Michael P.
author_facet Meacci, Giovanni
Wolfenson, Haguy
Liu, Shuaimin
Stachowiak, Matthew R.
Iskratsch, Thomas
Mathur, Anurag
Ghassemi, Saba
Gauthier, Nils
Tabdanov, Erdem
Lohner, James
Gondarenko, Alexander
Chander, Ashok C.
Roca-Cusachs, Pere
O’Shaughnessy, Ben
Hone, James
Sheetz, Michael P.
author_sort Meacci, Giovanni
collection PubMed
description 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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spelling pubmed-52215812017-01-22 α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions Meacci, Giovanni Wolfenson, Haguy Liu, Shuaimin Stachowiak, Matthew R. Iskratsch, Thomas Mathur, Anurag Ghassemi, Saba Gauthier, Nils Tabdanov, Erdem Lohner, James Gondarenko, Alexander Chander, Ashok C. Roca-Cusachs, Pere O’Shaughnessy, Ben Hone, James Sheetz, Michael P. Mol Biol Cell Articles 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. The American Society for Cell Biology 2016-11-07 /pmc/articles/PMC5221581/ /pubmed/27122603 http://dx.doi.org/10.1091/mbc.E16-02-0107 Text en © 2016 Meacci, Wolfenson, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Meacci, Giovanni
Wolfenson, Haguy
Liu, Shuaimin
Stachowiak, Matthew R.
Iskratsch, Thomas
Mathur, Anurag
Ghassemi, Saba
Gauthier, Nils
Tabdanov, Erdem
Lohner, James
Gondarenko, Alexander
Chander, Ashok C.
Roca-Cusachs, Pere
O’Shaughnessy, Ben
Hone, James
Sheetz, Michael P.
α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions
title α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions
title_full α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions
title_fullStr α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions
title_full_unstemmed α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions
title_short α-Actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions
title_sort α-actinin links extracellular matrix rigidity-sensing contractile units with periodic cell-edge retractions
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221581/
https://www.ncbi.nlm.nih.gov/pubmed/27122603
http://dx.doi.org/10.1091/mbc.E16-02-0107
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