Organization and dynamics of cross-linked actin filaments in confined environments
Organization and dynamics of cross-linked actin filaments in confined environments
复制标题
有限环境中交联肌动蛋白丝的组织和动力学
DOI：
10.1016/j.bpj.2022.11.2944
复制
发表时间：
2023
影响因子：
3.4
通讯作者：
Abel, Steven M.
中科院分区：
文献类型：
--
作者：
Akenuwa, Oghosa H.;Abel, Steven M.
肌动蛋白细胞骨架的组织受到物理限制、交联蛋白的特征和半柔性肌动蛋白丝的变形之间的相互作用的影响。一些交联蛋白优先结合平行的细丝，尽管其他的结合更不加选择。然而，如何结合的模式影响肌动蛋白网络在密闭环境中的组装缺乏定量的了解。在这里，我们采用粗粒度的计算机模拟研究的动力学和组织的半柔性肌动蛋白丝在封闭的区域后，加入交联剂。我们表征了系统形状、交联蛋白的数量和类型以及细丝的长度如何影响涌现行为。结构包括孤立的细丝簇，高度连接的细丝束，以及互连的束和环的网络。系统的一个维度的伸长促进与伸长轴对齐的长束的形成。动态是由快速交联成聚集体，其次是在他们的形状和连接缓慢的变化。交联通过抑制形状波动来降低短的或稀疏连接的长丝的平均弯曲能。然而，它增加了高度连接的网络中的平均弯曲能，因为丝束变形，并且少量的细丝表现出长寿命的、非常不利的构型。不加选择的交联促进了高能构型的形成，这是由于在早期不利的、难以松弛的构型的可能性增加。总之，这项工作证明了交联剂结合和物理限制影响肌动蛋白网络的涌现行为的物理机制，这在细胞和合成环境中都是相关的。
The organization of the actin cytoskeleton is impacted by the interplay between physical confinement, features of cross-linking proteins, and deformations of semiflexible actin filaments. Some cross-linking proteins preferentially bind filaments in parallel, although others bind more indiscriminately. However, a quantitative understanding of how the mode of binding influences the assembly of actin networks in confined environments is lacking. Here we employ coarse-grained computer simulations to study the dynamics and organization of semiflexible actin filaments in confined regions upon the addition of cross-linkers. We characterize how the emergent behavior is influenced by the system shape, the number and type of cross-linking proteins, and the length of filaments. Structures include isolated clusters of filaments, highly connected filament bundles, and networks of interconnected bundles and loops. Elongation of one dimension of the system promotes the formation of long bundles that align with the elongated axis. Dynamics are governed by rapid cross-linking into aggregates, followed by a slower change in their shape and connectivity. Cross-linking decreases the average bending energy of short or sparsely connected filaments by suppressing shape fluctuations. However, it increases the average bending energy in highly connected networks because filament bundles become deformed, and small numbers of filaments exhibit long-lived, highly unfavorable configurations. Indiscriminate cross-linking promotes the formation of high-energy configurations due to the increased likelihood of unfavorable, difficult-to-relax configurations at early times. Taken together, this work demonstrates physical mechanisms by which cross-linker binding and physical confinement impact the emergent behavior of actin networks, which is relevant both in cells and in synthetic environments.