Department of Biological Sciences, Columbia University, New York, NY, USA.
EMBO J. 2010 Mar 17;29(6):1055-68. doi: 10.1038/emboj.2010.2. Epub 2010 Feb 11.
Extracellular matrices in vivo are heterogeneous structures containing gaps that cells bridge with an actomyosin network. To understand the basis of bridging, we plated cells on surfaces patterned with fibronectin (FN)-coated stripes separated by non-adhesive regions. Bridges developed large tensions where concave cell edges were anchored to FN by adhesion sites. Actomyosin complexes assembled near those sites (both actin and myosin filaments) and moved towards the centre of the non-adhesive regions in a treadmilling network. Inhibition of myosin-II (MII) or Rho-kinase collapsed bridges, whereas extension continued over adhesive areas. Inhibition of actin polymerization (latrunculin-A, jasplakinolide) also collapsed the actomyosin network. We suggest that MII has distinct functions at different bridge regions: (1) at the concave edges of bridges, MIIA force stimulates actin filament assembly at adhesions and (2) in the body of bridges, myosin cross-links actin filaments and stimulates actomyosin network healing when breaks occur. Both activities ensure turnover of actin networks needed to maintain stable bridges from one adhesive region to another.
细胞外基质在体内是异质结构，含有细胞通过肌动球蛋白网络桥接的间隙。为了了解桥接的基础，我们将细胞种植在纤连蛋白 (FN) 涂层条纹的表面图案上，这些条纹由非粘性区域隔开。在凹面细胞边缘通过粘附位点与 FN 锚定的地方，桥形成了大的张力。肌动球蛋白复合物在这些位点附近组装（肌动蛋白和肌球蛋白丝），并在踏车网络中向非粘性区域的中心移动。肌球蛋白 II (MII) 或 Rho 激酶的抑制会使桥塌陷，而在粘附区域上的延伸则会继续。肌动蛋白聚合的抑制（Latrunculin-A，jasplakinolide）也会使肌动球蛋白网络崩溃。我们认为 MII 在不同的桥接区域有不同的功能：(1) 在桥的凹面边缘，MIIA 力刺激粘附处的肌动蛋白丝组装，(2) 在桥的主体中，肌球蛋白交联肌动蛋白丝，并在发生断裂时刺激肌动球蛋白网络的修复。这两种活性都确保了肌动蛋白网络的周转率，以维持从一个粘附区域到另一个粘附区域的稳定桥梁。
