title: Fibroblast polarization is a matrix-rigidity-dependent process controlled by focal adhesion mechanosensing.
abstract: Cell elongation and polarization are basic morphogenetic responses to extracellular matrix adhesion. We demonstrate here that human cultured fibroblasts readily polarize when plated on rigid, but not on compliant, substrates. On rigid surfaces, large and uniformly oriented focal adhesions are formed, whereas cells plated on compliant substrates form numerous small and radially oriented adhesions. Live-cell monitoring showed that focal adhesion alignment precedes the overall elongation of the cell, indicating that focal adhesion orientation may direct cell polarization. siRNA-mediated knockdown of 85 human protein tyrosine kinases (PTKs) induced distinct alterations in the cell polarization response, as well as diverse changes in cell traction force generation and focal adhesion formation. Remarkably, changes in rigidity-dependent traction force development, or focal adhesion mechanosensing, were consistently accompanied by abnormalities in the cell polarization response. We propose that the different stages of cell polarization are regulated by multiple, PTK-dependent molecular checkpoints that jointly control cell contractility and focal-adhesion-mediated mechanosensing.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Masha
authors.initials: M
authors.lastname: Prager-Khoutorsky
authors.forename: Alexandra
authors.initials: A
authors.lastname: Lichtenstein
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Krishnan
authors.forename: Kavitha
authors.initials: K
authors.lastname: Rajendran
authors.forename: Avi
authors.initials: A
authors.lastname: Mayo
authors.forename: Zvi
authors.initials: Z
authors.lastname: Kam
authors.forename: Benjamin
authors.initials: B
authors.lastname: Geiger
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Bershadsky
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000737:chemistry; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D005109:Extracellular Matrix / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D022001:Focal Adhesions / Q000502:physiology*; D005898:Glass / Q000737:chemistry; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009757:Nylons / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry; D034741:RNA, Small Interfering / Q000494:pharmacology; D013314:Stress, Mechanical
chemical_list: C529115:3-(pyridin-3-yl)acrylaldehyde; D004129:Dimethylpolysiloxanes; D009757:Nylons; D011725:Pyridines; D034741:RNA, Small Interfering; C085707:poly(dimethylsiloxane)-polyamide copolymer; D000171:Acrolein; D011505:Protein-Tyrosine Kinases
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