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Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting.
Mol Biol Cell 2019; 30(16):1974-1984MB

Abstract

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.

Authors+Show Affiliations

Biological Design Center, Department of Biomedical Engineering, Boston University, Boston, MA 02215.Biological Design Center, Department of Biomedical Engineering, Boston University, Boston, MA 02215.Biological Design Center, Department of Biomedical Engineering, Boston University, Boston, MA 02215.Biological Design Center, Department of Biomedical Engineering, Boston University, Boston, MA 02215.Department of Mechanical, Aerospace and Nuclear Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180.Department of Mechanical, Aerospace and Nuclear Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180. The Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, TX 78712.Biological Design Center, Department of Biomedical Engineering, Boston University, Boston, MA 02215.Biological Design Center, Department of Biomedical Engineering, Boston University, Boston, MA 02215.Department of Mechanical, Aerospace and Nuclear Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180. Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, CA 90007.Biological Design Center, Department of Biomedical Engineering, Boston University, Boston, MA 02215. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.Biological Design Center, Department of Biomedical Engineering, Boston University, Boston, MA 02215. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31318321

Citation

Yoon, Christine, et al. "Myosin IIA-mediated Forces Regulate Multicellular Integrity During Vascular Sprouting." Molecular Biology of the Cell, vol. 30, no. 16, 2019, pp. 1974-1984.
Yoon C, Choi C, Stapleton S, et al. Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting. Mol Biol Cell. 2019;30(16):1974-1984.
Yoon, C., Choi, C., Stapleton, S., Mirabella, T., Howes, C., Dong, L., ... Chen, C. S. (2019). Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting. Molecular Biology of the Cell, 30(16), pp. 1974-1984. doi:10.1091/mbc.E19-02-0076.
Yoon C, et al. Myosin IIA-mediated Forces Regulate Multicellular Integrity During Vascular Sprouting. Mol Biol Cell. 2019 Jul 22;30(16):1974-1984. PubMed PMID: 31318321.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting. AU - Yoon,Christine, AU - Choi,Colin, AU - Stapleton,Sarah, AU - Mirabella,Teodelinda, AU - Howes,Caroline, AU - Dong,Li, AU - King,Jessica, AU - Yang,Jinling, AU - Oberai,Assad, AU - Eyckmans,Jeroen, AU - Chen,Christopher S, Y1 - 2019/07/18/ PY - 2019/7/19/pubmed PY - 2019/7/19/medline PY - 2019/7/19/entrez SP - 1974 EP - 1984 JF - Molecular biology of the cell JO - Mol. Biol. Cell VL - 30 IS - 16 N2 - 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. SN - 1939-4586 UR - https://www.unboundmedicine.com/medline/citation/31318321/Myosin_IIA-mediated_forces_regulate_multicellular_integrity_during_vascular_sprouting L2 - https://www.molbiolcell.org/doi/full/10.1091/mbc.E19-02-0076?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -