The role of nonmuscle myosin 2A and 2B in the regulation of mesenchymal cell contact guidance

Alexander S. Zhovmer, Erdem D. Tabdanov, Houxun Miao, Han Wen, Jinqiu Chen, Xiaoling Luo, Xuefei Ma, Paolo P. Provenzano, Robert S. Adelstein

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Contact guidance refers to the ability of cells to sense the geometrical features of the microenvironment and respond by changing their shape and adopting the appropriate orientation. Inhibition and ablation of nonmuscle myosin 2 (NM2) paralogues have demonstrated their importance for contact guidance. However, the specific roles of the NM2 paralogues have not been systematically studied. In this work we use micropatterned substrates to examine the roles of NM2A and NM2B and to elucidate the relationship of the microenvironment, actomyosin, and microtubules in contact guidance. We show that contact guidance is preserved following loss of NM2B and that expression of NM2A alone is sufficient to establish an appropriate orientation of the cells. Loss of NM2B and overexpression of NM2A result in a prominent cell polarization that is found to be linked to the increased alignment of microtubules with the actomyosin scaffold. Suppression of actomyosin with blebbistatin reduces cell polarity on a flat surface, but not on a surface with contact guidance cues. This indicates that the lost microtubule–actomyosin interactions are compensated for by microtubule–mi-croenvironment interactions, which are sufficient to establish cell polarity through contact guidance.

Original languageEnglish (US)
Pages (from-to)1961-1973
Number of pages13
JournalMolecular biology of the cell
Issue number16
StatePublished - Jul 22 2019

Bibliographical note

Funding Information:
This work was enhanced by advice from Sachiyo Kawamoto and Mary Anne Conti (National Heart, Lung, and Blood Institute [NHLBI]); Tatyana Svitkina (University of Pennsylvania); Bridgette Heine, Kem A. Sochacki, and Justin W. Taraska (NHLBI); and Christian Combs and Daniela Malide (NHLBI). It was supported by the NHLBI Division of Intramural Research (HL006209), a Research Scholar Grant, RSG-14-171-01-CSM, from the American Cancer Society to P.P.P., and the National Institutes of Health (R01CA181385 and U54CA210190 University of Minnesota Physical Sciences in Oncology Center to P.P.P.).

Publisher Copyright:
© 2019 Zhovmer et al.


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