Bathe Mark, Heussinger Claus, Claessens Mireille M A E, Bausch Andreas R, Frey Erwin
Arnold Sommerfeld Zentrum für Theoretische Physik and Center for NanoScience, Ludwig-Maximilians-Universität München, Munich, Germany.
Biophys J. 2008 Apr 15;94(8):2955-64. doi: 10.1529/biophysj.107.119743. Epub 2007 Nov 30.
The mechanical properties of cytoskeletal actin bundles play an essential role in numerous physiological processes, including hearing, fertilization, cell migration, and growth. Cells employ a multitude of actin-binding proteins to actively regulate bundle dimensions and cross-linking properties to suit biological function. The mechanical properties of actin bundles vary by orders of magnitude depending on diameter and length, cross-linking protein type and concentration, and constituent filament properties. Despite their importance to cell function, the molecular design principles responsible for this mechanical behavior remain unknown. Here, we examine the mechanics of cytoskeletal bundles using a molecular-based model that accounts for the discrete nature of constituent actin filaments and their distinct cross-linking proteins. A generic competition between filament stretching and cross-link shearing determines three markedly different regimes of mechanical response that are delineated by the relative values of two simple design parameters, revealing the universal nature of bundle-bending mechanics. In each regime, bundle-bending stiffness displays distinct scaling behavior with respect to bundle dimensions and molecular composition, as observed in reconstituted actin bundles in vitro. This mechanical behavior has direct implications on the physiological bending, buckling, and entropic stretching behavior of cytoskeletal processes, as well as reconstituted actin systems. Results are used to predict the bending regimes of various in vivo cytoskeletal bundles that are not easily accessible to experiment and to generate hypotheses regarding implications of the isolated behavior on in vivo bundle function.
细胞骨架肌动蛋白束的力学性质在众多生理过程中发挥着至关重要的作用,这些生理过程包括听力、受精、细胞迁移和生长。细胞利用多种肌动蛋白结合蛋白来积极调节束的尺寸和交联特性,以适应生物学功能。肌动蛋白束的力学性质根据直径和长度、交联蛋白类型和浓度以及组成细丝的性质而在多个数量级上变化。尽管它们对细胞功能很重要,但导致这种力学行为的分子设计原理仍然未知。在这里,我们使用基于分子的模型来研究细胞骨架束的力学,该模型考虑了组成肌动蛋白细丝及其不同交联蛋白的离散性质。细丝拉伸和交联剪切之间的一般竞争决定了三种明显不同的力学响应模式,这些模式由两个简单设计参数的相对值来界定,揭示了束弯曲力学的普遍性质。在每种模式下,束弯曲刚度相对于束尺寸和分子组成表现出不同的标度行为,这在体外重构的肌动蛋白束中也有观察到。这种力学行为对细胞骨架过程以及重构的肌动蛋白系统的生理弯曲、屈曲和熵拉伸行为有直接影响。研究结果用于预测各种体内细胞骨架束的弯曲模式,这些模式不易通过实验获得,并生成关于孤立行为对体内束功能影响的假设。