INSIGHTS INTO THE MECHANICS OF CYTOKINETIC RING ASSEMBLY USING 3D MODELING.
INSIGHTS INTO THE MECHANICS OF CYTOKINETIC RING ASSEMBLY USING 3D MODELING.
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使用 3D 建模深入了解细胞动力学环组装的机制。
DOI：
10.1115/imece2014-39006
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Vavylonis,Dimitrios
中科院分区：
文献类型：
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作者：
Bidone,TamaraCarla;Tang,Haosu;Vavylonis,Dimitrios
在分裂酵母胞质分裂，肌动蛋白丝成核的皮层神经元Cdc 12被捕获的肌球蛋白马达绑定到一个带的皮层节点。肌球蛋白马达施加力将节点拉到一起形成收缩环。交联的相互作用有助于将肌动蛋白丝和节点排列成一束。肌球蛋白运动域的突变以及交联剂α-辅肌动蛋白和纤维蛋白浓度的变化会改变凝聚网络的形态，导致团块、环或延伸的网状结构。环形成过程中的收缩张力如何取决于网络形态、肌球蛋白运动活性、交联和肌动蛋白丝周转之间的相互作用仍有待阐明。我们使用一个3D计算模型来解决这个问题，在这个模型中，半柔性肌动蛋白丝（表示为由弹簧连接的珠子）从formins中生长出来，可以被邻近节点中的肌球蛋白捕获，并通过吸引力相互作用相互交联。我们确定了一组广泛的条件下，肌球蛋白动力学和肌动蛋白丝之间的交联强度的连接节点之间的张力产生的制度。我们找到最大限度地提高周向张力的条件，将它们与网络形态相关联，并提出实验来测试这些预测。这项工作解决了“软质和活物质的形态发生”，使用计算建模来模拟细胞动力学环组件的粘弹性交联肌动蛋白网络，包括活性分子马达的关键分子机制。
During fission yeast cytokinesis, actin filaments nucleated by cortical formin Cdc12 are captured by myosin motors bound to a band of cortical nodes. The myosin motors exert forces that pull nodes together into a contractile ring. Cross-linking interactions help align actin filaments and nodes into a single bundle. Mutations in the myosin motor domain and changes in the concentration of cross-linkers alpha-actinin and fimbrin alter the morphology of the condensing network, leading to clumps, rings or extended meshworks. How the contractile tension developing during ring formation depends on the interplay between network morphology, myosin motor activity, cross-linking and actin filament turnover remains to be elucidated. We addressed this question using a 3D computational model in which semiflexible actin filaments (represented as beads connected by springs) grow from formins, can be captured by myosin in neighboring nodes, and get cross-linked with one another through an attractive interaction. We identify regimes of tension generation between connected nodes under a wide set of conditions regarding myosin dynamics and strength of cross-linking between actin filaments. We find conditions that maximize circumferential tension, correlate them with network morphology and propose experiments to test these predictions. This work addresses “Morphogenesis of soft and living matter” using computational modeling to simulate cytokinetic ring assembly from the key molecular mechanisms of viscoelastic cross-linked actin networks that include active molecular motors.