Crawling from soft to stiff matrix polarizes the cytoskeleton and phosphoregulates myosin-II heavy chain

Matthew Raab, Joe Swift, P. C Dave P Dingal, Palak Shah, Jae Won Shin, Dennis E. Discher

    Research output: Contribution to journalArticlepeer-review

    Abstract

    On rigid surfaces, the cytoskeleton of migrating cells is polarized, but tissue matrix is normally soft. We show that nonmuscleMIIB (myosin-IIB) is unpolarized in cells on soft matrix in 2D and also within soft 3D collagen, with rearward polarization of MIIBemerging only as cells migrate from soft to stiff matrix. Durotaxis is the tendency of cells to crawl from soft to stiff matrix, and durotaxis of primary mesenchymal stem cells (MSCs) proved more sensitive to MIIB than to the more abundant and persistently unpolarized nonmuscle MIIA (myosin-IIA). However, MIIA has a key upstream role: in cells on soft matrix, MIIA appeared diffuse and mobile, whereas on stiff matrix, MIIA was strongly assembled in oriented stress fibers that MIIB then polarized. The difference was caused inpart by elevated phospho-S1943-MIIA in MSCs on soft matrix, with site-specific mutants revealing the importance of phosphomoderated assembly of MIIA. Polarization is thus shown to be a highly regulated compass for mechanosensitive migration. © 2012 Raab et al.
    Original languageEnglish
    Pages (from-to)669-683
    Number of pages14
    JournalJournal of Cell Biology
    Volume199
    Issue number4
    DOIs
    Publication statusPublished - Nov 2012

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