Force-exerting perpendicular lateral protrusions in fibroblastic cell contraction

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dc.contributor.authorPadhi, Abinashen
dc.contributor.authorSingh, Karanpreeten
dc.contributor.authorFranco-Barraza, Januszen
dc.contributor.authorMarston, Daniel J.en
dc.contributor.authorCukierman, Ednaen
dc.contributor.authorHahn, Klaus M.en
dc.contributor.authorKapania, Rakesh K.en
dc.contributor.authorNain, Amrinder S.en
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentAerospace and Ocean Engineeringen
dc.date.accessioned2020-11-11T14:28:58Zen
dc.date.available2020-11-11T14:28:58Zen
dc.date.issued2020-07-21en
dc.description.abstractAligned extracellular matrix fibers enable fibroblasts to undergo myofibroblastic activation and achieve elongated shapes. Activated fibroblasts are able to contract, perpetuating the alignment of these fibers. This poorly understood feedback process is critical in chronic fibrosis conditions, including cancer. Here, using fiber networks that serve as force sensors, we identify "3D perpendicular lateral protrusions" (3D-PLPs) that evolve from lateral cell extensions named twines. Twines originate from stratification of cyclic-actin waves traversing the cell and swing freely in 3D to engage neighboring fibers. Once engaged, a lamellum forms and extends multiple secondary twines, which fill in to form a sheet-like PLP, in a force-entailing process that transitions focal adhesions to activated (i.e., pathological) 3D-adhesions. The specific morphology of PLPs enables cells to increase contractility and force on parallel fibers. Controlling geometry of extracellular networks confirms that anisotropic fibrous environments support 3D-PLP formation and function, suggesting an explanation for cancer-associated desmoplastic expansion. Padhi et al. employ nanofibers with controlled structure and alignment as an extra-cellular matrix model, on which they study the exertion of forces from adherent fibroblasts. Identifying force exerting 3D perpendicular lateral protrusions, authors describe a mechanism which leads to the contraction of parallel, neighbouring fibers, and the forces needed to move and align the neighbouring fibers. These findings have relevance in understanding cancer-associated desmoplastic expansion.en
dc.description.notesA.S.N., E.C., and K.M.H. are thankful to the late Professor Patricia Keely (University of Wisconsin) for discussions and guidance on cell biology and dedicate this paper to her. This work is supported by National Science Foundation (1762634) awarded to A.S.N. and K.M.H., by GM-R35GM122596 awarded to K.M.H. E.C. is funded by gifts donated to the memory of Judy Costin, Jeanne Leinen philanthropic donation, Marianne DiNofrio Pancreatic Research Foundation, funds from the Martin and Concetta Greenberg Pancreatic cancer Institute (Fox Chase Cancer Center), Pennsylvania's DOH Health Research Formula Funds, the Greenfield Foundation, the 5th AHEPA Cancer Research Foundation, Inc., the Worldwide Cancer Research Fox Chase In Vino Vita Institutional Pilot Award, as well as NIH/NCI grants R21-CA231252 and R01-CA232256, and the Fox Chase Core grant CA06927. A.S.N. would also like to acknowledge the Institute of Critical Technologies and Sciences (ICTAS) and Macro-molecules Innovative Institute at Virginia Tech for their support in conducting this study. A.P. and A.S.N. would like to thank members of the STEP Lab for their helpful suggestions and discussions.en
dc.description.sponsorshipNational Science FoundationNational Science Foundation (NSF) [1762634]; Martin and Concetta Greenberg Pancreatic cancer Institute (Fox Chase Cancer Center); Pennsylvania's DOH Health Research Formula Funds; Greenfield Foundation; 5th AHEPA Cancer Research Foundation, Inc.; Worldwide Cancer Research Fox Chase In Vino Vita Institutional Pilot Award; NIH/NCIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [R21-CA231252, R01-CA232256]; Fox Chase Core grant [CA06927]; Institute of Critical Technologies and Sciences (ICTAS); Macro-molecules Innovative Institute at Virginia Tech; Marianne DiNofrio Pancreatic Research Foundation; [GM-R35GM122596]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s42003-020-01117-7en
dc.identifier.eissn2399-3642en
dc.identifier.issue1en
dc.identifier.other390en
dc.identifier.pmid32694539en
dc.identifier.urihttp://hdl.handle.net/10919/100833en
dc.identifier.volume3en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleForce-exerting perpendicular lateral protrusions in fibroblastic cell contractionen
dc.title.serialCommunications Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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