Actin filament mechanics and branched network turnover

摘要 肌动蛋白细丝组装成Arp2/3复合分支细丝网络的能力 真核生物的基本细胞过程，包括运动、内吞和胞质分裂。委员会成员 肌动蛋白解聚因子同源(ADF-H)结构域蛋白家族，包括粘连蛋白和胶质细胞 成熟因子(GMF)，加速分支肌动蛋白细丝网络的重组和周转。Cofilin和 GMF通过解支Arp 2/3复合体加速网络重构。Cofilin通过以下方式加速网络周转 在亚基增加和解离的地方，碎裂细丝和增加细丝的浓度结束。 这一米拉方案结合了生化和生物物理方法，包括电子冷冻显微镜， 微流体学和最近开发的微型磁柱分析，以开发预测模型 肌动蛋白细丝和细丝网络的力学、重塑和断裂。关于以下方面的一般原则： 肌动蛋白细丝弹性、构象和调节蛋白占有率之间的关系将从 这项工作。

SUMMARY The assembly of actin filaments into Arp2/3 complex-branched filament networks powers numerous fundamental eukaryotic cellular processes, including motility, endocytosis, and cytokinesis. Members of the actin depolymerization factor homology (ADF-H)-domain protein family, which includes cofilin and glial maturation factor (GMF), accelerate branched actin filament network reorganization and turnover. Cofilin and GMF accelerate network remodeling by debranching Arp 2/3 complex. Cofilin accelerates network turnover by fragmenting filaments and increasing the concentration of filament ends where subunits add and dissociate. This MIRA proposal integrates biochemical and biophysical approaches, including electron cryo-microscopy, microfluidics, and a recently developed microscopic magnetic cylinders assay, to develop predictive models of actin filament and filament network mechanics, remodeling and fragmentation. General principles regarding the relationship between actin filament elasticity, conformation and regulatory protein occupancy will emerge from this work.