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Endothelial cell sensing, restructuring, and invasion in collagen hydrogel structures

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dc.contributor.authorHosseini, Yahyaen
dc.contributor.authorAgah, Masouden
dc.contributor.authorVerbridge, Scott S.en
dc.contributor.departmentElectrical and Computer Engineeringen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.date.accessed2016-03-17en
dc.date.accessioned2016-03-18T22:24:53Zen
dc.date.available2016-03-18T22:24:53Zen
dc.date.issued2015-09-03en
dc.description.abstractExperimental tools to model cell-tissue interactions will likely lead to new ways to both understand and treat cancer. While the mechanical properties and regulation of invasion have been recently studied for tumor cells, they have received less attention in the context of tumor vascular dynamics. In this article, we have investigated the interaction between the surfaces of structures encountered by endothelial cells invading their surrounding extracellular matrix (ECM) during angiogenesis. For this purpose, we have fabricated round and sharp geometries with various curvature and sharpness indices in collagen hydrogel over a wide range of stiffness to mimic different microenvironments varying from normal to tumor tissues. We have then cultured endothelial cells on these structures to investigate the bi-directional interaction between the cells and ECM. We have observed that cell invasion frequency is higher from the structures with the highest sharpness and curvature index, while interestingly the dependence of invasion on the local micro-geometry is strongest for the highest density matrices. Notably, structures with the highest invasion length are linked with higher deformation of side structures, which may be related to traction force-activated signaling suggesting further investigation. We have noted that round structures are more favorable for cell adhesion and in some cases round structures drive cell invasion faster than sharp ones. These results highlight the ability of endothelial cells to sense small variations in ECM geometry, and respond with a balance of matrix invasion as well as deformation, with potential implications for feedback mechanisms that may enhance vascular abnormality in response to tumor-induced ECM alterations.en
dc.description.notes2015 Royal Society of Chemistry Open Access Gold Articleen
dc.description.sponsorshipVirginia Tech. Institute for Critical Technology and Applied Scienceen
dc.description.sponsorshipNational Science Foundation (U.S.)en
dc.description.sponsorshipNational Institutes of Health (U.S.)en
dc.format.extent10 p.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHosseini, Y., Agah, M., & Verbridge, S. S. (2015). Endothelial cell sensing, restructuring, and invasion in collagen hydrogel structures. Integrative Biology, 7(11), 1432-1441. doi:10.1039/C5IB00207Aen
dc.identifier.doihttps://doi.org/10.1039/C5IB00207Aen
dc.identifier.issn1757-9694en
dc.identifier.issue11en
dc.identifier.other2015_Hosseini_Endothelial_cell_sensing_restru.pdfen
dc.identifier.otherCBET-1403304en
dc.identifier.otherNIBIB-R21EB019123en
dc.identifier.urihttp://hdl.handle.net/10919/64953en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherThe Royal Society of Chemistryen
dc.rightsCreative Commons Attribution-NonCommercial 3.0 Unporteden
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en
dc.titleEndothelial cell sensing, restructuring, and invasion in collagen hydrogel structuresen
dc.title.serialIntegrative Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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