Molecular clutch drives cell response to surface viscosity.
Molecular clutch drives cell response to surface viscosity.
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DOI：
10.1073/pnas.1710653115
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发表时间：
2018-02-06
影响因子：
11.1
通讯作者：
Salmeron-Sanchez M
中科院分区：
文献类型：
--
作者：
Bennett M;Cantini M;Reboud J;Cooper JM;Roca-Cusachs P;Salmeron-Sanchez M
组织本质上是粘弹性的，其物理特性在发育、肿瘤发生和伤口愈合中发挥着重要作用。细胞对基质弹性的反应通过“分子离合器”得到了很好的理解，当刚度足够高以暴露机械敏感蛋白中的结合位点时，分子离合器就会接合。在这里，我们表明细胞对纯粘性表面（即没有弹性成分）的反应可以通过相同的分子离合器来解释。细胞用来感知刚性的机制更加通用，可用于揭示细胞与复杂粘弹性环境的相互作用。该研究提供了一种了解组织内细胞的工具，进而开辟了将粘度纳入合成细胞微环境设计的新途径。细胞对基质刚性的反应可以通过肌动蛋白-肌动蛋白-整合素-纤连蛋白离合器的机械特性来解释。这里，分子离合器模型被扩展以解释细胞与纯粘性表面（即没有弹性部件）的相互作用。支持的脂质双层提供了一个理想化且可控的系统，通过它来研究这一概念。使用不同扩散系数的脂质，所呈现的配体（在本例中为RGD）的迁移率（即表面粘度）发生了一个数量级的改变。细胞大小和细胞骨架组织与粘度成正比。此外，在移动性较差（粘性较大）的表面上，粘着斑数量较多，FAK 磷酸化程度较高。肌动蛋白逆行流是施加在表面上的力的指标，在移动性更强的表面上也被发现更快。这会对下游分子产生间接影响；机械敏感的 YAP 蛋白在移动性较小（粘性较大）的表面上更多地定位于细胞核，并且成肌细胞的分化在较高的粘性下增强。这种行为在分子离合器模型的框架内得到了解释，较低的粘度导致较低的力加载速率，防止机械敏感蛋白质的暴露，而较高的粘度导致较高的力加载速率暴露这些位点，激活下游通路。因此，了解粘度（无论基质刚度如何）如何影响细胞响应，为设计控制细胞行为的材料提供了进一步的工具。
Tissues are viscoelastic in nature and their physical properties play a fundamental role in development, tumorigenesis, and wound healing. Cell response to matrix elasticity is well understood through a “molecular clutch” which engages when stiffness is sufficiently high to expose binding sites in mechanosensitive proteins. Here we show that cell response to pure viscous surfaces (i.e., with no elastic component) can be explained through the same molecular clutch. Mechanisms used by cells to sense rigidity are more universal and can be used to unveil cell interaction with complex viscoelastic environments. The research presents a tool to understand cells within tissues and in turn opens new avenues to incorporate viscosity into the design of synthetic cellular microenvironments. Cell response to matrix rigidity has been explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. Here the molecular clutch model is extended to account for cell interactions with purely viscous surfaces (i.e., without an elastic component). Supported lipid bilayers present an idealized and controllable system through which to study this concept. Using lipids of different diffusion coefficients, the mobility (i.e., surface viscosity) of the presented ligands (in this case RGD) was altered by an order of magnitude. Cell size and cytoskeletal organization were proportional to viscosity. Furthermore, there was a higher number of focal adhesions and a higher phosphorylation of FAK on less-mobile (more-viscous) surfaces. Actin retrograde flow, an indicator of the force exerted on surfaces, was also seen to be faster on more mobile surfaces. This has consequential effects on downstream molecules; the mechanosensitive YAP protein localized to the nucleus more on less-mobile (more-viscous) surfaces and differentiation of myoblast cells was enhanced on higher viscosity. This behavior was explained within the framework of the molecular clutch model, with lower viscosity leading to a low force loading rate, preventing the exposure of mechanosensitive proteins, and with a higher viscosity causing a higher force loading rate exposing these sites, activating downstream pathways. Consequently, the understanding of how viscosity (regardless of matrix stiffness) influences cell response adds a further tool to engineer materials that control cell behavior.
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影响因子：
16.6
作者：
Chaudhuri O;Gu L;Darnell M;Klumpers D;Bencherif SA;Weaver JC;Huebsch N;Mooney DJ
通讯作者：
Mooney DJ
DOPC和DPPC的制备支持原子力显微镜和原子力光谱的平面脂质双层。
影响因子：
5.6
作者：
Attwood SJ;Choi Y;Leonenko Z
通讯作者：
Leonenko Z
DOI：
10.1021/acs.langmuir.5b03259
发表时间：
2016-01-26
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
--
作者：
Bathawab F;Bennett M;Cantini M;Reboud J;Dalby MJ;Salmerón-Sánchez M
通讯作者：
Salmerón-Sánchez M
影响因子：
3.7
作者：
HUGHES, BD;PAILTHORPE, BA;WHITE, LR
通讯作者：
WHITE, LR
影响因子：
3.4
作者：
Brizuela Guerra, Nayrim;Gonzalez-Garcia, Cristina;Salmeron-Sanchez, Manuel
通讯作者：
Salmeron-Sanchez, Manuel