Vinculin Facilitates Cell Invasion into Three-dimensional Collagen Matrices
The cytoskeletal protein vinculin contributes to the mechanical link of the contractile actomyosin cytoskeleton to the extracellular matrix (ECM) through integrin receptors. In addition, vinculin modulates the dynamics of cell adhesions and is associated with decreased cell motility on two-dimension...
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creator | Mierke, Claudia T. Kollmannsberger, Philip Zitterbart, Daniel Paranhos Diez, Gerold Koch, Thorsten M. Marg, Susanna Ziegler, Wolfgang H. Goldmann, Wolfgang H. Fabry, Ben |
description | The cytoskeletal protein vinculin contributes to the mechanical link of the contractile actomyosin cytoskeleton to the extracellular matrix (ECM) through integrin receptors. In addition, vinculin modulates the dynamics of cell adhesions and is associated with decreased cell motility on two-dimensional ECM substrates. The effect of vinculin on cell invasion through dense three-dimensional ECM gels is unknown. Here, we report how vinculin expression affects cell invasion into three-dimensional collagen matrices. Cell motility was investigated in vinculin knockout and vinculin expressing wild-type mouse embryonic fibroblasts. Vinculin knockout cells were 2-fold more motile on two-dimensional collagen-coated substrates compared with wild-type cells, but 3-fold less invasive in 2.4 mg/ml three-dimensional collagen matrices. Vinculin knockout cells were softer and remodeled their cytoskeleton more dynamically, which is consistent with their enhanced two-dimensional motility but does not explain their reduced three-dimensional invasiveness. Importantly, vinculin-expressing cells adhered more strongly to collagen and generated 3-fold higher traction forces compared with vinculin knockout cells. Moreover, vinculin-expressing cells were able to migrate into dense (5.8 mg/ml) three-dimensional collagen matrices that were impenetrable for vinculin knockout cells. These findings suggest that vinculin facilitates three-dimensional matrix invasion through up-regulation or enhanced transmission of traction forces that are needed to overcome the steric hindrance of ECMs. |
doi_str_mv | 10.1074/jbc.M109.087171 |
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In addition, vinculin modulates the dynamics of cell adhesions and is associated with decreased cell motility on two-dimensional ECM substrates. The effect of vinculin on cell invasion through dense three-dimensional ECM gels is unknown. Here, we report how vinculin expression affects cell invasion into three-dimensional collagen matrices. Cell motility was investigated in vinculin knockout and vinculin expressing wild-type mouse embryonic fibroblasts. Vinculin knockout cells were 2-fold more motile on two-dimensional collagen-coated substrates compared with wild-type cells, but 3-fold less invasive in 2.4 mg/ml three-dimensional collagen matrices. Vinculin knockout cells were softer and remodeled their cytoskeleton more dynamically, which is consistent with their enhanced two-dimensional motility but does not explain their reduced three-dimensional invasiveness. Importantly, vinculin-expressing cells adhered more strongly to collagen and generated 3-fold higher traction forces compared with vinculin knockout cells. Moreover, vinculin-expressing cells were able to migrate into dense (5.8 mg/ml) three-dimensional collagen matrices that were impenetrable for vinculin knockout cells. These findings suggest that vinculin facilitates three-dimensional matrix invasion through up-regulation or enhanced transmission of traction forces that are needed to overcome the steric hindrance of ECMs.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M109.087171</identifier><identifier>PMID: 20181946</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Actin ; Animals ; Biophysics ; Cell Adhesion - physiology ; Cell Biology ; Cell Migration ; Cell Movement - physiology ; Cells, Cultured ; Collagen ; Collagen - metabolism ; Cytoskeleton ; Cytoskeleton - genetics ; Cytoskeleton - metabolism ; Embryo, Mammalian - cytology ; Embryo, Mammalian - metabolism ; Extracellular Matrix - genetics ; Extracellular Matrix - metabolism ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Focal Adhesions ; Magnetic Tweezers ; Mice ; Mice, Knockout ; Molecular Biophysics ; Prestress ; Steric Hindrance ; Tractions ; Vinculin - genetics ; Vinculin - metabolism</subject><ispartof>The Journal of biological chemistry, 2010-04, Vol.285 (17), p.13121-13130</ispartof><rights>2010 © 2010 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2010 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-5343ea85d5ca059582650589e2b082a51ff20ebc1e4a12016049f4f46257681f3</citedby><cites>FETCH-LOGICAL-c434t-5343ea85d5ca059582650589e2b082a51ff20ebc1e4a12016049f4f46257681f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857131/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857131/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20181946$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mierke, Claudia T.</creatorcontrib><creatorcontrib>Kollmannsberger, Philip</creatorcontrib><creatorcontrib>Zitterbart, Daniel Paranhos</creatorcontrib><creatorcontrib>Diez, Gerold</creatorcontrib><creatorcontrib>Koch, Thorsten M.</creatorcontrib><creatorcontrib>Marg, Susanna</creatorcontrib><creatorcontrib>Ziegler, Wolfgang H.</creatorcontrib><creatorcontrib>Goldmann, Wolfgang H.</creatorcontrib><creatorcontrib>Fabry, Ben</creatorcontrib><title>Vinculin Facilitates Cell Invasion into Three-dimensional Collagen Matrices</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The cytoskeletal protein vinculin contributes to the mechanical link of the contractile actomyosin cytoskeleton to the extracellular matrix (ECM) through integrin receptors. In addition, vinculin modulates the dynamics of cell adhesions and is associated with decreased cell motility on two-dimensional ECM substrates. The effect of vinculin on cell invasion through dense three-dimensional ECM gels is unknown. Here, we report how vinculin expression affects cell invasion into three-dimensional collagen matrices. Cell motility was investigated in vinculin knockout and vinculin expressing wild-type mouse embryonic fibroblasts. Vinculin knockout cells were 2-fold more motile on two-dimensional collagen-coated substrates compared with wild-type cells, but 3-fold less invasive in 2.4 mg/ml three-dimensional collagen matrices. Vinculin knockout cells were softer and remodeled their cytoskeleton more dynamically, which is consistent with their enhanced two-dimensional motility but does not explain their reduced three-dimensional invasiveness. Importantly, vinculin-expressing cells adhered more strongly to collagen and generated 3-fold higher traction forces compared with vinculin knockout cells. Moreover, vinculin-expressing cells were able to migrate into dense (5.8 mg/ml) three-dimensional collagen matrices that were impenetrable for vinculin knockout cells. These findings suggest that vinculin facilitates three-dimensional matrix invasion through up-regulation or enhanced transmission of traction forces that are needed to overcome the steric hindrance of ECMs.</description><subject>Actin</subject><subject>Animals</subject><subject>Biophysics</subject><subject>Cell Adhesion - physiology</subject><subject>Cell Biology</subject><subject>Cell Migration</subject><subject>Cell Movement - physiology</subject><subject>Cells, Cultured</subject><subject>Collagen</subject><subject>Collagen - metabolism</subject><subject>Cytoskeleton</subject><subject>Cytoskeleton - genetics</subject><subject>Cytoskeleton - metabolism</subject><subject>Embryo, Mammalian - cytology</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Extracellular Matrix - genetics</subject><subject>Extracellular Matrix - metabolism</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Focal Adhesions</subject><subject>Magnetic Tweezers</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular Biophysics</subject><subject>Prestress</subject><subject>Steric Hindrance</subject><subject>Tractions</subject><subject>Vinculin - genetics</subject><subject>Vinculin - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1PGzEQhi1UBGng3FvZP7DB449d7wWpikiLGsSBD3GzHO9sMHK8kb1E6r-vowUEB3wZyfPMO6OHkB9AZ0Brcf68srNroM2MqhpqOCAToIqXXMLjNzKhlEHZMKmOyfeUnml-ooEjcswoKGhENSF_H1ywL96FYmGs824wA6Zijt4XV2FnkutD4cLQF3dPEbFs3QbD_tP4Yt57b9YYimszRGcxnZDDzviEp691Su4Xl3fzP-Xy5vfV_NeytIKLoZRccDRKttIaKhupWCWpVA2yFVXMSOg6RnFlAYWBfGmVj-5EJyom60pBx6fkYszdvqw22FoMQzReb6PbmPhP98bpz53gnvS632mmZA0ccsD5GGBjn1LE7n0WqN571dmr3nvVo9c88fPjynf-TWQGzkagM7026-iSvr_NXZ4BpnilMtGMBGY1O4dRJ-swWGxdRDvotndfrv8PMYKQ6g</recordid><startdate>20100423</startdate><enddate>20100423</enddate><creator>Mierke, Claudia T.</creator><creator>Kollmannsberger, Philip</creator><creator>Zitterbart, Daniel Paranhos</creator><creator>Diez, Gerold</creator><creator>Koch, Thorsten M.</creator><creator>Marg, Susanna</creator><creator>Ziegler, Wolfgang H.</creator><creator>Goldmann, Wolfgang H.</creator><creator>Fabry, Ben</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20100423</creationdate><title>Vinculin Facilitates Cell Invasion into Three-dimensional Collagen Matrices</title><author>Mierke, Claudia T. ; Kollmannsberger, Philip ; Zitterbart, Daniel Paranhos ; Diez, Gerold ; Koch, Thorsten M. ; Marg, Susanna ; Ziegler, Wolfgang H. ; Goldmann, Wolfgang H. ; Fabry, Ben</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-5343ea85d5ca059582650589e2b082a51ff20ebc1e4a12016049f4f46257681f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Actin</topic><topic>Animals</topic><topic>Biophysics</topic><topic>Cell Adhesion - physiology</topic><topic>Cell Biology</topic><topic>Cell Migration</topic><topic>Cell Movement - physiology</topic><topic>Cells, Cultured</topic><topic>Collagen</topic><topic>Collagen - metabolism</topic><topic>Cytoskeleton</topic><topic>Cytoskeleton - genetics</topic><topic>Cytoskeleton - metabolism</topic><topic>Embryo, Mammalian - cytology</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Extracellular Matrix - genetics</topic><topic>Extracellular Matrix - metabolism</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Focal Adhesions</topic><topic>Magnetic Tweezers</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Molecular Biophysics</topic><topic>Prestress</topic><topic>Steric Hindrance</topic><topic>Tractions</topic><topic>Vinculin - genetics</topic><topic>Vinculin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mierke, Claudia T.</creatorcontrib><creatorcontrib>Kollmannsberger, Philip</creatorcontrib><creatorcontrib>Zitterbart, Daniel Paranhos</creatorcontrib><creatorcontrib>Diez, Gerold</creatorcontrib><creatorcontrib>Koch, Thorsten M.</creatorcontrib><creatorcontrib>Marg, Susanna</creatorcontrib><creatorcontrib>Ziegler, Wolfgang H.</creatorcontrib><creatorcontrib>Goldmann, Wolfgang H.</creatorcontrib><creatorcontrib>Fabry, Ben</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mierke, Claudia T.</au><au>Kollmannsberger, Philip</au><au>Zitterbart, Daniel Paranhos</au><au>Diez, Gerold</au><au>Koch, Thorsten M.</au><au>Marg, Susanna</au><au>Ziegler, Wolfgang H.</au><au>Goldmann, Wolfgang H.</au><au>Fabry, Ben</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vinculin Facilitates Cell Invasion into Three-dimensional Collagen Matrices</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2010-04-23</date><risdate>2010</risdate><volume>285</volume><issue>17</issue><spage>13121</spage><epage>13130</epage><pages>13121-13130</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The cytoskeletal protein vinculin contributes to the mechanical link of the contractile actomyosin cytoskeleton to the extracellular matrix (ECM) through integrin receptors. In addition, vinculin modulates the dynamics of cell adhesions and is associated with decreased cell motility on two-dimensional ECM substrates. The effect of vinculin on cell invasion through dense three-dimensional ECM gels is unknown. Here, we report how vinculin expression affects cell invasion into three-dimensional collagen matrices. Cell motility was investigated in vinculin knockout and vinculin expressing wild-type mouse embryonic fibroblasts. Vinculin knockout cells were 2-fold more motile on two-dimensional collagen-coated substrates compared with wild-type cells, but 3-fold less invasive in 2.4 mg/ml three-dimensional collagen matrices. Vinculin knockout cells were softer and remodeled their cytoskeleton more dynamically, which is consistent with their enhanced two-dimensional motility but does not explain their reduced three-dimensional invasiveness. Importantly, vinculin-expressing cells adhered more strongly to collagen and generated 3-fold higher traction forces compared with vinculin knockout cells. Moreover, vinculin-expressing cells were able to migrate into dense (5.8 mg/ml) three-dimensional collagen matrices that were impenetrable for vinculin knockout cells. These findings suggest that vinculin facilitates three-dimensional matrix invasion through up-regulation or enhanced transmission of traction forces that are needed to overcome the steric hindrance of ECMs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20181946</pmid><doi>10.1074/jbc.M109.087171</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Actin Animals Biophysics Cell Adhesion - physiology Cell Biology Cell Migration Cell Movement - physiology Cells, Cultured Collagen Collagen - metabolism Cytoskeleton Cytoskeleton - genetics Cytoskeleton - metabolism Embryo, Mammalian - cytology Embryo, Mammalian - metabolism Extracellular Matrix - genetics Extracellular Matrix - metabolism Fibroblasts - cytology Fibroblasts - metabolism Focal Adhesions Magnetic Tweezers Mice Mice, Knockout Molecular Biophysics Prestress Steric Hindrance Tractions Vinculin - genetics Vinculin - metabolism |
title | Vinculin Facilitates Cell Invasion into Three-dimensional Collagen Matrices |
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