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dc.contributor.authorLee, Sunyoung
dc.contributor.authorZeiger, Adam Scott
dc.contributor.authorMaloney, John M.
dc.contributor.authorKotecki, Maciej
dc.contributor.authorVan Vliet, Krystyn J.
dc.contributor.authorHerman, Ira M.
dc.date.accessioned2011-06-15T15:44:18Z
dc.date.available2011-06-15T15:44:18Z
dc.date.issued2010-04
dc.date.submitted2009-11
dc.identifier.issn0953-8984
dc.identifier.urihttp://hdl.handle.net/1721.1/64441
dc.description.abstractPericytes physically surround the capillary endothelium, contacting and communicating with associated vascular endothelial cells via cell–cell and cell–matrix contacts. Pericyte–endothelial cell interactions thus have the potential to modulate growth and function of the microvasculature. Here we employ the experimental finding that pericytes can buckle a freestanding, underlying membrane via actin-mediated contraction. Pericytes were cultured on deformable silicone substrata, and pericyte-generated wrinkles were imaged via both optical and atomic force microscopy (AFM). The local stiffness of subcellular domains both near and far from these wrinkles was investigated by using AFM-enabled nanoindentation to quantify effective elastic moduli. Substratum buckling contraction was quantified by the normalized change in length of initially flat regions of the substrata (corresponding to wrinkle contour lengths), and a model was used to relate local strain energies to pericyte contractile forces. The nature of pericyte-generated wrinkling and contractile protein-generated force transduction was further explored by the addition of pharmacological cytoskeletal inhibitors that affected contractile forces and the effective elastic moduli of pericyte domains. Actin-mediated forces are sufficient for pericytes to exert an average buckling contraction of 38% on the elastomeric substrata employed in these in vitro studies. Actomyosin-mediated contractile forces also act in vivo on the compliant environment of the microvasculature, including the basement membrane and other cells. Pericyte-generated substratum deformation can thus serve as a direct mechanical stimulus to adjacent vascular endothelial cells, and potentially alter the effective mechanical stiffness of nonlinear elastic extracellular matrices, to modulate pericyte–endothelial cell interactions that directly influence both physiologic and pathologic angiogenesis.en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (CAREER Award)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (Chemical, Bioengineering, Environmental, and Transport Systems-0644846)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (EY 19533)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (EY 15125)en_US
dc.language.isoen_US
dc.publisherInstitute of Physicsen_US
dc.relation.isversionofhttp://dx.doi.org/10.1088/0953-8984/22/19/194115en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourceMIT web domainen_US
dc.titlePericyte actomyosin-mediated contraction at the cell-material interface can modulate the microvascular nicheen_US
dc.typeArticleen_US
dc.identifier.citationLee, Sunyoung et al. "Pericyte actomyosin-mediated contraction at the cell-material interface can modulate the microvascular niche." 2010 J. Phys.: Condens. Matter 22 194115.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Materials Science and Engineeringen_US
dc.contributor.approverVan Vliet, Krystyn J.
dc.contributor.mitauthorVan Vliet, Krystyn J.
dc.contributor.mitauthorLee, Sunyoung
dc.contributor.mitauthorZeiger, Adam Scott
dc.contributor.mitauthorMaloney, John M.
dc.relation.journalJournal of Phyics: Condensed Matteren_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLee, Sunyoung; Zeiger, Adam; Maloney, John M; Kotecki, Maciej; Van Vliet, Krystyn J; Herman, Ira Men
dc.identifier.orcidhttps://orcid.org/0000-0001-5735-0560
dc.identifier.orcidhttps://orcid.org/0000-0002-6853-811X
dspace.mitauthor.errortrue
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


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