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In contrast, elongated cells migrating inside dermal explants and the cell-derived matrix (CDM) formed blunt, cylindrical protrusions, termed lobopodia, and Rac1, Cdc42, and PIP3 signaling was nonpolarized. Reducing RhoA, Rho-associated protein kinase (ROCK), or myosin II activity switched the cells to lamellipodia-based 3D migration. These modes of 3D migration were regulated by matrix physical properties. Specifically, experimentally modifying the elasticity of the CDM or collagen gels established that nonlinear elasticity supported lamellipodia-based migration, whereas linear elasticity switched cells to lobopodia-based migration. Thus, the relative polarization of intracellular signaling identifies two distinct modes of 3D cell migration governed intrinsically by RhoA, ROCK, and myosin II and extrinsically by the elastic behavior of the 3D extracellular matrix.<\/jats:p>","DOI":"10.1083\/jcb.201201124","type":"journal-article","created":{"date-parts":[[2012,4,30]],"date-time":"2012-04-30T11:49:01Z","timestamp":1335786541000},"page":"439-455","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":364,"title":["Nonpolarized signaling reveals two distinct modes of 3D cell migration"],"prefix":"10.1083","volume":"197","author":[{"given":"Ryan J.","family":"Petrie","sequence":"first","affiliation":[{"name":"Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research 1 ; and 2"},{"name":"Auditory Mechanics Section, National Institute on Deafness and Other Communication Disorders; National Institutes of Health, Bethesda, MD 20892 1 ; and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Gavara","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research 1 ; and 2"},{"name":"Auditory Mechanics Section, National Institute on Deafness and Other Communication Disorders; National Institutes of Health, Bethesda, MD 20892 1 ; and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Chadwick","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research 1 ; and 2"},{"name":"Auditory Mechanics Section, National Institute on Deafness and Other Communication Disorders; National Institutes of Health, Bethesda, MD 20892 1 ; and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Yamada","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research 1 ; and 2"},{"name":"Auditory Mechanics Section, National Institute on Deafness and Other Communication Disorders; National Institutes of Health, Bethesda, MD 20892 1 ; and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2012,4,30]]},"reference":[{"key":"2023072302110169600_bib1","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1016\/j.biomaterials.2006.12.030","article-title":"Biomechanical and biochemical characteristics of a human fibroblast-produced and remodeled matrix","volume":"28","author":"Ahlfors","year":"2007","journal-title":"Biomaterials."},{"key":"2023072302110169600_bib2","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1002\/jcp.1041350313","article-title":"Extracellular matrix assembly of cell-derived and plasma-derived fibronectins by substrate-attached fibroblasts","volume":"135","author":"Allio","year":"1988","journal-title":"J. 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