Non-monotonic dependence of stiffness on actin crosslinking in cytoskeleton composites

Non-monotonic dependence of stiffness on actin crosslinking in cytoskeleton composites
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DOI:
10.1039/c9sm01550g
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发表时间:
2019-11-28
期刊:
影响因子:
3.4
通讯作者:
Robertson-Anderson, Rae M.
Robertson-Anderson, Rae M.
中科院分区:
化学2区
文献类型:
--
作者:
Francis, Madison L.;Ricketts, Shea N.;Robertson-Anderson, Rae M.

文献摘要

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细胞骨架能够通过半柔性肌动蛋白丝、刚性微管和一套交联蛋白之间的相互作用精确地调整其结构和力学。然而,这些组件中的每一个的作用,以及它们之间的相互作用,在复合细胞骨架的动力学中发挥的作用仍然是一个悬而未决的问题。在这里,我们使用光镊微观流变学和荧光共聚焦显微镜揭示了令人惊讶的方式,其中肌动蛋白交联调谐肌动蛋白微管复合材料的粘弹性和流动性从稳态到高度非线性制度。虽然先前的研究已经表明,增加肌动蛋白网络中的交联会增加弹性和刚度,但我们发现复合材料的刚度对肌动蛋白交联表现出显著的非单调依赖性-首先增加,然后降低到与未连接的复合材料相似或甚至更低的响应。我们进一步表明,肌动蛋白交联对微管的流动性有着意想不到的强烈影响;事实上,微管的流动性-由交联剂驱动的肌动蛋白丝重排决定-控制着复合材料的刚度。这一结果与肌动蛋白运动驱动细胞骨架力学的传统思想不一致。更一般地说,我们的结果表明,当交联复合材料以赋予强度和弹性时,更多并不总是更好。
The cytoskeleton is able to precisely tune its structure and mechanics through interactions between semiflexible actin filaments, rigid microtubules and a suite of crosslinker proteins. However, the role that each of these components, as well as the interactions between them, plays in the dynamics of the composite cytoskeleton remains an open question. Here, we use optical tweezers microrheology and fluorescence confocal microscopy to reveal the surprising ways in which actin crosslinking tunes the viscoelasticity and mobility of actin-microtubule composites from steady-state to the highly nonlinear regime. While previous studies have shown that increasing crosslinking in actin networks increases elasticity and stiffness, we instead find that composite stiffness displays a striking non-monotonic dependence on actin crosslinking - first increasing then decreasing to a response similar to or even lower than un-linked composites. We further show that actin crosslinking has an unexpectedly strong impact on the mobility of microtubules; and it is in fact the microtubule mobility - dictated by crosslinker-driven rearrangements of actin filaments - that controls composite stiffness. This result is at odds with conventional thought that actin mobility drives cytoskeleton mechanics. More generally, our results demonstrate that - when crosslinking composite materials to confer strength and resilience - more is not always better.