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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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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. |
format | Online Article Text |
id | pubmed-5221581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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