Theoretical modeling on mechanochemical feedbacks of cellular processes

细胞过程机械化学反馈的理论模型

• 批准号: 8158042
• 负责人: Jian Liu
• 金额: $ 49.51万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8158042
• 关键词: Cell physiology; Theoretical model

1. Membrane Trafficking: In this project, we investigated the functional role of the BAR and F-BAR domain proteins in yeast endocytosis. Our research showed that cooperation between robust actin polymerization, and F-BAR and BAR domain proteins, and synaptojanin, is important for membrane scission. Spatio-temporal and functional information together with our theoretical modeling suggest the following picture of endocytosis: F-BAR proteins stabilize the endocytic site, while actin assembly and BAR proteins cooperate for invagination and scission. This paper is currently under review for publication. 2. Kinetochore motility: Based on the histogram of the neighboring distance between kinetochore ring along microtubule, I contructed a statistical model to differentiate whether the rings can diffuse or not. Our research shows that kinetochore ring must be highly diffusive. The paper is currently in preparation for publication. 3. Asymmetric Furrow ingression during cytokinesis: We construct a minimal model on the contractility of actomyosin ring during cytokinesis. Our model proposes that the local geometry of the furrow site, such as the Gaussian curvature of the membrane, could promote the alignment process of actomyosin filament, which in turn governs the efficiency of the local contractility. As the more the local actomyosin filament contracts, the larger the local Gaussian curvature would become. We show that this mechanism can quantitatively account for all the three modes of actomyosin contractility, depending on the coupling strength of the positive feedback between the local membrane curvature and actomyosin contractility. More importantly, our experimental testing corroborates several predictions unique to our model, suggesting an emergent mechanism of curvature-mediated positive feedback for cytokinetic actomyosin contractility. Furthermore, the model demonstrate that asymmetric furrow ingression is energetically more efficient, thereby suggesting a real functional role of the asymmetry in cytokinetic ring contraction. This model is the first of its kinds. This paper is currently in preparation for publication.

1。膜贩运： 在这个项目中，我们研究了棒和F-BAR结构蛋白在酵母内吞作用中的功能作用。 我们的研究表明，鲁棒肌动蛋白聚合，F-BAR和BAR结构域蛋白质以及突触素蛋白之间的合作对于膜分裂很重要。 时空和功能信息以及我们的理论建模表明，内吞作用：F-BAR蛋白稳定内吞位点，而肌动蛋白组装和BAR蛋白合作以进行内脏和刻度。 本文目前正在审查出版。 2。动力学运动： 基于沿微管沿着动齿环之间的相邻距离的直方图，我创建了一个统计模型，以区分环是否可以扩散。 我们的研究表明，动力学环必须是高度扩散的。 该论文目前正在准备出版。 3。细胞因子期间的不对称沟进气： 我们构建了一个关于肌动球蛋白期间肌动蛋白环的收缩力的最小模型。 我们的模型提出，犁沟部位的局部几何形状，例如膜的高斯曲率，可以促进肌动蛋白丝的比对过程，从而控制局部收缩效率。 随着局部肌动蛋白丝合同的越多，局部高斯曲率就会越大。 我们表明，该机制可以定量解释Actomyosin收缩力的所有三种模式，具体取决于局部膜曲率和肌动蛋白收缩性之间正反馈的耦合强度。 更重要的是，我们的实验测试证实了我们的模型所特有的几种预测，这表明曲率介导的呈曲率介导的阳性反馈的紧急机制是细胞动力学肌动蛋白收缩力。 此外，该模型表明，不对称的犁沟在能量上更有效，从而提出了不对称性在细胞动力学环收缩中的实际功能作用。 该模型是同类的第一种。 本文目前正在准备出版。