Aligned fibers direct collective cell migration to engineer closing and nonclosing wound gaps

Puja Sharma, Colin Ng, Aniket Jana, Abinash Padhi, Paige Szymanski, Jerry S.H. Lee, Bahareh Behkam, Amrinder S. Nain*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Cell 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 μm 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.

Original languageEnglish
Pages (from-to)2579-2588
Number of pages10
JournalMolecular Biology of the Cell
Issue number19
StatePublished - 15 Sep 2017
Externally publishedYes


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