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dc.contributor.authorYoon, Christineen_US
dc.contributor.authorChoi, Colinen_US
dc.contributor.authorStapleton, Sarahen_US
dc.contributor.authorMirabella, Teodelindaen_US
dc.contributor.authorHowes, Carolineen_US
dc.contributor.authorDong, Lien_US
dc.contributor.authorKing, Jessicaen_US
dc.contributor.authorYang, Jinlingen_US
dc.contributor.authorOberai, Assaden_US
dc.contributor.authorEyckmans, Jeroenen_US
dc.contributor.authorChen, Christopher S.en_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2020-04-14T17:37:36Z
dc.date.available2020-04-14T17:37:36Z
dc.date.issued2019-07-22
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/31318321
dc.identifier.citationChristine Yoon, Colin Choi, Sarah Stapleton, Teodelinda Mirabella, Caroline Howes, Li Dong, Jessica King, Jinling Yang, Assad Oberai, Jeroen Eyckmans, Christopher S Chen. 2019. "Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting.." Mol Biol Cell, Volume 30, Issue 16, pp. 1974 - 1984. https://doi.org/10.1091/mbc.E19-02-0076
dc.identifier.issn1939-4586
dc.identifier.urihttps://hdl.handle.net/2144/40148
dc.description.abstractAngiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell-cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified as controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this question, we investigated the role of cellular contractility in sprout morphogenesis, using a biomimetic model of angiogenesis. Three-dimensional maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell-cell dissociation primarily between tip and stalk cells. Closer examination of cell-cell junctions revealed that blebbistatin impaired adherens-junction organization, particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell-cell adhesions during collective motility.en_US
dc.description.sponsorshipR01 EB000262 - NIBIB NIH HHS; R01 HL115553 - NHLBI NIH HHSen_US
dc.format.extentp. 1974 - 1984en_US
dc.languageeng
dc.language.isoen_US
dc.relation.ispartofMol Biol Cell
dc.rights2019 Yoon, Choi, Stapleton, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0
dc.subjectAnimalsen_US
dc.subjectBiomechanical phenomenaen_US
dc.subjectCell adhesionen_US
dc.subjectCell movementen_US
dc.subjectHEK293 cellsen_US
dc.subjectHuman umbilical vein endothelial cellsen_US
dc.subjectHumansen_US
dc.subjectMice, inbred C57BLen_US
dc.subjectMorphogenesisen_US
dc.subjectNeovascularization, physiologicen_US
dc.subjectNonmuscle myosin type IIAen_US
dc.subjectProtein isoformsen_US
dc.subjectDevelopmental biologyen_US
dc.subjectBiological sciencesen_US
dc.subjectMedical and health sciencesen_US
dc.titleMyosin IIA-mediated forces regulate multicellular integrity during vascular sproutingen_US
dc.typeArticleen_US
dc.description.versionPublished versionen_US
dc.identifier.doi10.1091/mbc.E19-02-0076
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Engineeringen_US
pubs.organisational-groupBoston University, College of Engineering, Department of Biomedical Engineeringen_US
pubs.publication-statusPublisheden_US
dc.identifier.orcid0000-0003-1475-8149 (Eyckmans, Jeroen)
dc.identifier.orcid0000-0003-2445-8449 (Chen, Christopher S)
dc.identifier.mycv482173


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2019 Yoon, Choi, Stapleton, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.
Except where otherwise noted, this item's license is described as 2019 Yoon, Choi, Stapleton, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License.