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dc.contributor.authorSharma, Pujaen
dc.contributor.authorNg, Colinen
dc.contributor.authorJana, Aniketen
dc.contributor.authorPadhi, Abinashen
dc.contributor.authorSzymanski, Paigeen
dc.contributor.authorLee, Jerry S. H.en
dc.contributor.authorBehkam, Baharehen
dc.contributor.authorNain, Amrinder S.en
dc.description.abstractCell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a crucial precursor to collective cell migration in wound closure and cancer metastasis, respectively. However, there is a fundamental gap in our quantitative understanding of the role of local ECM size and arrangement in cell emergence-based migration and local gap closure. Here, using ECM-mimicking nanofibers bridging cell monolayers, we describe a method to recapitulate and quantitatively describe these in vivo behaviors over multispatial (single cell to cell sheets) and temporal (minutes to weeks) scales. On fiber arrays with large interfiber spacing, cells emerge (invade) either singularly by breaking cell-cell junctions analogous to release of a stretched rubber band (recoil), or in groups of few cells (chains), whereas on closely spaced fibers, multiple chains emerge collectively. Advancing cells on fibers form cell streams, which support suspended cell sheets (SCS) of various sizes and curvatures. SCS converge to form local gaps that close based on both the gap size and shape. We document that cell stream spacing of 375 mu m and larger hinders SCS advancement, thus providing abilities to engineer closing and nonclosing gaps. Altogether we highlight the importance of studying cell-fiber interactions and matrix structural remodeling in fundamental and translational cell biology.en
dc.description.sponsorshipBill and Andrea Waide Research Fund (Roanoke, VA); National Science Foundation (NSF) [CMMI-1437101, CMMI-1462916]; NSF [CBET-1454226, 320463, 320464]; Institute of Critical Technology and Applied Sciences at Virginia Techen
dc.rightsCreative Commons Attribution-NonCommercial-ShareAlike 3.0 Unporteden
dc.titleAligned fibers direct collective cell migration to engineer closing and nonclosing wound gapsen
dc.typeArticle - Refereeden
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentSchool of Biomedical Engineering and Sciencesen
dc.description.notesWe thank Klaus Hahn (University of North Carolina) and Guy Genin (Washington University, St. Louis) for reading the article and providing critical feedback. We also thank Jon Jarvik (Carnegie Mellon University) for generously providing the NIH 3T3 cell line; AhRam Kim for her support with preliminary experiments; and Virginia Tech undergraduate volunteers Harrison Bolinger, Luke Grant, Giancarlo Di Base, Drew Smith, Ryan Grove, Liam Han, Mark Andrew Healy, and Yuxin Zheng, who helped in analyzing the data for overall gap closure (Figure 4A). We also thank James Mason Inder for help in generating Supplemental Movies 8, 9, and 14. This research was partially funded by the Bill and Andrea Waide Research Fund (Roanoke, VA), National Science Foundation (NSF) grants (CMMI-1437101 and CMMI-1462916) to A.S.N., an NSF CAREER award (CBET-1454226) to B.B., NSF REU awards (320463 and 320464), and the Institute of Critical Technology and Applied Sciences at Virginia Tech.en
dc.title.serialMolecular Biology of the Cellen

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Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported