Department of Physics and Biophysics, University of San Diego, 5998 Alcala Park, San Diego, CA 92110, USA.
Department of Physics, University of Massachusetts, Amherst, 666 N. Pleasant St., Amherst, MA 01003, USA.
Soft Matter. 2019 Nov 28;15(44):9056-9065. doi: 10.1039/c9sm01550g. Epub 2019 Oct 24.
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.
细胞骨架能够通过半刚性肌动蛋白丝、刚性微管和一系列交联蛋白之间的相互作用，精确地调整其结构和力学性质。然而，这些成分中的每一个，以及它们之间的相互作用，在复合细胞骨架动力学中所起的作用，仍然是一个悬而未决的问题。在这里，我们使用光镊微流变学和荧光共聚焦显微镜，揭示了肌动蛋白交联以出人意料的方式调节肌动蛋白-微管复合物从稳态到高度非线性状态的粘弹性和迁移率。虽然以前的研究表明，增加肌动蛋白网络中的交联会增加弹性和刚性，但我们发现，复合材料的刚性显示出显著的非单调依赖性于肌动蛋白交联-先增加然后减少到与未交联的复合材料相似甚至更低的响应。我们进一步表明，肌动蛋白交联对微管的迁移率有出乎意料的强烈影响；实际上，正是交联驱动的肌动蛋白丝重排决定了微管的迁移率，从而控制了复合材料的刚性。这一结果与传统观点相矛盾，即肌动蛋白的迁移率驱动细胞骨架力学。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。
