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Nonmuscle Myosin IIA-Dependent Force Inhibits Cell Spreading and Drives F-Actin Flow

Yunfei Cai ^*, Nicolas Biais ^*, Gregory Giannone ^*, Monica Tanase ^*, Guoying Jiang ^*, Jake M. Hofman , Chris H. Wiggins , Pascal Silberzan , Axel Buguin , Benoit Ladoux ^¶ and Michael P. Sheetz ^*

^* Department of Biological Sciences, and Department of Physics, Columbia University, New York, New York; Department of Applied Physics and Applied Mathematics, Center for Computational Biology and Bioinformatics, Columbia University, New York, New York; Physico-Chimie Curie, Unité Mixte de Recherche Centre National de la Recherche Scientifique 168, Institut Curie, Paris, France; and ^¶ Matière et Systèmes Complexes, CNRS UMR 7057/Université Paris 7, Paris, France

Correspondence: Address reprint requests to Dr. Michael P. Sheetz, Dept. of Biological Sciences, Columbia University, Sherman Fairchild Center, Rm. 713, 1212 Amsterdam Ave., New York, NY 10027. Tel.: 212-854-4857; Fax: 212-854-6399; E-mail: ms2001{at}columbia.edu.

Nonmuscle myosin IIA (NMM-IIA) is involved in the formation of focal adhesions and neurite retraction. However, the role of NMM-IIA in these functions remains largely unknown. Using RNA interference as a tool to decrease NMM-IIA expression, we have found that NMM-IIA is the major myosin involved in traction force generation and retrograde F-actin flow in mouse embryonic fibroblast cells. Quantitative analyses revealed that 60% of traction force on fibronectin-coated surfaces is contributed by NMM-IIA and 30% by NMM-IIB. The retrograde F-actin flow decreased dramatically in NMM-IIA-depleted cells, but seemed unaffected by NMM-IIB deletion. In addition, we found that depletion of NMM-IIA caused cells to spread at a higher rate and to a greater area on fibronectin substrates during the early spreading period, whereas deletion of NMM-IIB appeared to have no effect on spreading. The distribution of NMM-IIA was concentrated on the dorsal surface and approached the ventral surface in the periphery, whereas NMM-IIB was primarily concentrated around the nucleus and to a lesser extent at the ventral surface in cell periphery. Our results suggest that NMM-IIA is involved in generating a coherent cytoplasmic contractile force from one side of the cell to the other through the cross-linking and the contraction of dorsal actin filaments.

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