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 BAR 和 F-BAR 结构域蛋白在酵母内吞作用中的功能作用。 我们的研究表明，强大的肌动蛋白聚合、F-BAR 和 BAR 结构域蛋白以及突触贾蛋白之间的合作对于膜断裂非常重要。 时空和功能信息与我们的理论模型一起表明了以下内吞作用的图景：F-BAR 蛋白稳定内吞位点，而肌动蛋白组装和 BAR 蛋白配合内陷和分裂。 该论文目前正在审查出版中。 2.着丝粒运动： 根据动粒环沿微管的相邻距离的直方图，我构建了一个统计模型来区分环是否可以扩散。 我们的研究表明动粒环一定是高度扩散的。 该论文目前正在准备出版。 3. 胞质分裂过程中不对称的沟槽侵入： 我们构建了胞质分裂期间肌动球蛋白环收缩性的最小模型。 我们的模型提出，沟位的局部几何形状，例如膜的高斯曲率，可以促进肌动球蛋白丝的排列过程，进而控制局部收缩性的效率。 随着局部肌动球蛋白丝收缩得越多，局部高斯曲率就会变得越大。 我们表明，这种机制可以定量地解释肌动球蛋白收缩性的所有三种模式，具体取决于局部膜曲率和肌动球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模型特有的几个预测，表明曲率介导的细胞因子肌动球蛋白收缩性正反馈的新兴机制。 此外，该模型表明，不对称沟进入在能量上更有效，从而表明不对称性在细胞因子环收缩中的真正功能作用。 该模型是此类模型中的第一个。 这篇论文目前正在准备出版。