Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting
Chen, Christopher S.
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Citation (published version)Christine 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
Angiogenic 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.
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.