title: Actin flow and talin dynamics govern rigidity sensing in actin-integrin linkage through talin extension.
abstract: At cell-substrate adhesion sites, the linkage between actin filaments and integrin is regulated by mechanical stiffness of the substrate. Of potential molecular regulators, the linker proteins talin and vinculin are of particular interest because mechanical extension of talin induces vinculin binding with talin, which reinforces the actin-integrin linkage. For understanding the molecular and biophysical mechanism of rigidity sensing at cell-substrate adhesion sites, we constructed a simple physical model to examine a role of talin extension in the stiffness-dependent regulation of actin-integrin linkage. We show that talin molecules linking between retrograding actin filaments and substrate-bound integrin are extended in a manner dependent on substrate stiffness. The model predicts that, in adhesion complexes containing ≈30 talin links, talin is extended enough for vinculin binding when the substrate is stiffer than 1 kPa. The lifetime of talin links needs to be 2-5 s to achieve an appropriate response of talin extension against substrate stiffness. Furthermore, changes in actin velocity drastically shift the range of substrate stiffness that induces talin-vinculin binding. Our results suggest that talin extension is a key step in sensing and responding to substrate stiffness at cell adhesion sites.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hirata
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore A*STAR Bioinformatics Institute, Singapore 138671, Singapore chiamkh@bii.a-star.edu.sg.
authors.forename: Keng-Hwee
authors.initials: KH
authors.lastname: Chiam
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore Department of Biomedical Engineering, National University of Singapore, Singapore 117576, Singapore Department of Mechanical Engineering, National University of Singapore, Singapore 117576, Singapore.
authors.forename: Chwee Teck
authors.initials: CT
authors.lastname: Lim
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore Mechanobiology Laboratory, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan msokabe@med.nagoya-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sokabe
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008954:Models, Biological; D013499:Surface Properties; D016608:Talin / Q000378:metabolism*; D016596:Vinculin / Q000378:metabolism
chemical_list: D000199:Actins; D016023:Integrins; D016608:Talin; D016596:Vinculin
keywords: focal adhesion; mechanosensor; mechanotransduction; substrate stiffness; talin; vinculin