Substrate compliance versus ligand density in cell on gel responses
Substrate compliance versus ligand density in cell on gel responses
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DOI：
10.1016/s0006-3495(04)74140-5
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发表时间：
2004-01-01
影响因子：
3.4
通讯作者：
Discher, D
中科院分区：
文献类型：
--
作者：
Engler, A;Bacakova, L;Discher, D
基质硬度正在成为许多细胞类型响应中的重要物理因素。与其他锚定依赖性细胞系的研究结果一致，发现主动脉平滑肌细胞在“硬”玻璃或“硬”凝胶上比在“软”凝胶上更能扩散和组织其细胞骨架和粘着斑。尽管这些细胞通常在中等胶原密度上显示出最大的铺展，但在软凝胶上的有限铺展令人惊讶地对粘附配体密度不敏感。钟形细胞扩展曲线涵盖所有基板的简单功能，耦合配体密度基板刚度建模。尽管平滑肌细胞在软凝胶上的扩散最小，而不管胶原蛋白，但GFP-肌动蛋白给出了总肌动蛋白的轻微过表达，其可以覆盖软凝胶反应并驱动扩散; GFP和GFP-桩蛋白不具有相同的效果。GFP-肌动蛋白细胞总是显示出有组织的丝状细胞骨架，并清楚地表明细胞骨架是信号网络中的至少一个结构节点，可以超越通常由软凝胶决定的扩散限制。基于这样的结果，我们假设一个中央结构的作用，细胞骨架在驱动膜向外扩展过程中，而粘附加强了扩展。
Substrate stiffness is emerging as an important physical factor in the response of many cell types. In agreement with findings on other anchorage-dependent cell lineages, aortic smooth muscle cells are found to spread and organize their cytoskeleton and focal adhesions much more so on "rigid'' glass or "stiff'' gels than on "soft'' gels. Whereas these cells generally show maximal spreading on intermediate collagen densities, the limited spreading on soft gels is surprisingly insensitive to adhesive ligand density. Bell-shaped cell spreading curves encompassing all substrates are modeled by simple functions that couple ligand density to substrate stiffness. Although smooth muscle cells spread minimally on soft gels regardless of collagen, GFP-actin gives a slight overexpression of total actin that can override the soft gel response and drive spreading; GFP and GFP-paxillin do not have the same effect. The GFP-actin cells invariably show an organized filamentous cytoskeleton and clearly indicate that the cytoskeleton is at least one structural node in a signaling network that can override spreading limits typically dictated by soft gels. Based on such results, we hypothesize a central structural role for the cytoskeleton in driving the membrane outward during spreading whereas adhesion reinforces the spreading.