Please use this identifier to cite or link to this item: https://doi.org/10.1021/nn304966z
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dc.titleNanotopography modulates mechanotransduction of stem cells and induces differentiation through focal adhesion kinase
dc.contributor.authorTeo, B.K.K.
dc.contributor.authorWong, S.T.
dc.contributor.authorLim, C.K.
dc.contributor.authorKung, T.Y.S.
dc.contributor.authorYap, C.H.
dc.contributor.authorRamagopal, Y.
dc.contributor.authorRomer, L.H.
dc.contributor.authorYim, E.K.F.
dc.date.accessioned2014-10-08T09:46:02Z
dc.date.available2014-10-08T09:46:02Z
dc.date.issued2013-06-25
dc.identifier.citationTeo, B.K.K., Wong, S.T., Lim, C.K., Kung, T.Y.S., Yap, C.H., Ramagopal, Y., Romer, L.H., Yim, E.K.F. (2013-06-25). Nanotopography modulates mechanotransduction of stem cells and induces differentiation through focal adhesion kinase. ACS Nano 7 (6) : 4785-4798. ScholarBank@NUS Repository. https://doi.org/10.1021/nn304966z
dc.identifier.issn19360851
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/87973
dc.description.abstractRegulated biophysical cues, such as nanotopography, have been shown to be integral for tissue regeneration and embryogenesis in the stem cell niche. Tissue homeostasis involves the interaction of multipotent cells with nanoscaled topographical features in their ECM to regulate aspects of cell behavior. Synthetic nanostructures can drive specific cell differentiation, but the sensing mechanisms for nanocues remain poorly understood. Here, we report that nanotopography-induced human mesenchymal stem cell (hMSC) differentiation through cell mechanotransduction is modulated by the integrin-activated focal adhesion kinase (FAK). On nanogratings with 250 nm line width on polydimethylsiloxane, hMSCs developed aligned stress fibers and showed an upregulation of neurogenic and myogenic differentiation markers. The observed cellular focal adhesions within these cells were also significantly smaller and more elongated on the nanogratings compared to microgratings or unpatterned control. In addition, our mechanistic study confirmed that this regulation was dependent upon actomyosin contractility, suggesting a direct force-dependent mechanism. The topography-induced differentiation was observed on different ECM compositions but the response was not indicative of a direct ECM-induced hMSC differentiation pathway. FAK phosphorylation was required for topography-induced hMSC differentiation while FAK overexpression overruled the topographical cues in determining cell lineage bias. The results indicated that FAK activity had a direct impact on topography-induced gene expression, and that this effect of FAK was independent of cell shape. These findings suggest that hMSC sense and transduce nanotopographical signals through focal adhesions and actomyosin cytoskeleton contractility to induce differential gene expression. © 2013 American Chemical Society.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1021/nn304966z
dc.sourceScopus
dc.subjectcell signaling
dc.subjectdifferentiation
dc.subjectFAK
dc.subjectfocal adhesions
dc.subjectmesenchymal stem cell
dc.subjectnanotopography
dc.subjectphysical cues
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.contributor.departmentBIOENGINEERING
dc.description.doi10.1021/nn304966z
dc.description.sourcetitleACS Nano
dc.description.volume7
dc.description.issue6
dc.description.page4785-4798
dc.identifier.isiut000321093800011
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