NSF-ANR: Molecular Control of Actin Cortex Organization and Phase Transitions

本项目的基本目标是揭示控制细胞肌动蛋白皮层组装和组织的分子机制。肌动蛋白皮层是连接细胞膜的肌动蛋白丝和肌球蛋白马达组成的薄网络，其结构和组织调节着细胞在迁移、分裂和形态发生过程中的形状变化。虽然皮层的关键分子成分已经被表征，但它们如何组装和维持不同的肌动蛋白网络组织仍然知之甚少。该合作项目旨在通过将新的多尺度建模工具与体外实验技术相结合，了解皮层组装的多尺度动力学，这将有利于研究细胞生物学，生物物理学和机械生物学的研究人员群体。这项合作将为博士后和学生提供最先进的模拟和实验技术培训，在多学科和刺激的环境中，他们将在那里合作和发展国际专业网络。从该项目中吸取的经验教训将被整合到PI开发的生物物理学研究生和本科生课程中，以展示自组织生物系统如何从分子组分之间的相互作用中产生。该项目旨在开发新的实验方法来操纵重组肌动蛋白网络中的组装，周转和力产生。与此同时，研究人员将为大脑皮层建立一个多尺度模型，整合分子尺度上的数据，生成网络尺度上的预测，并将进行实验测试。利用这些工具，研究人员旨在构建类似皮层的肌动球蛋白网络，这种网络可以动态地转变成不同的组织。第二个目标是确定皮层肌动蛋白网络的机械化学性质如何在分子尺度上进行调整，以驱动不同产生力的肌动蛋白结构之间的转换。该项目旨在通过展示不同的肌动蛋白网络，而不是独立构建，在皮层内机械集成并通过相变出现，从而改变当前的范式。这个美国/法国合作项目由美国国家科学基金会和法国国家研究机构支持，其中美国国家科学基金会资助美国研究者，法国国家研究机构资助法国合作伙伴。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The fundamental goal of this project is to uncover the molecular mechanisms controlling the assembly and organization of the cellular actin cortex. The actin cortex is a thin network of actin filaments and myosin motors coupled to the cell membrane, whose structure and organization regulate cell shape changes during migration, division, and morphogenesis. While the key molecular components of the cortex have been characterized, how they assemble and maintain diverse actin network organizations remain poorly understood. This collaborative project aims to understand the multi-scale dynamics of cortex assembly by integrating new multi-scale modeling tools with in vitro experimental techniques, which will benefit the communities of researchers studying cell biology, biophysics and mechanobiology. This collaboration will provide training in state-of-the-art simulation and experimental techniques to postdocs and students, in multidisciplinary and stimulating environments, where they will collaborate and develop international professional networks. Lessons learnt from this project will be integrated into graduate and undergraduate curriculum in Biophysics developed by the PI, to demonstrate how self-organized biological systems emerge from the interaction between molecular components.This project aims to develop new experimental approaches to manipulate the assembly, turnover, and force generation in reconstituted actin networks. In parallel, the researchers will build a multi-scale model for the cortex, integrating data at the molecular scale to generate predictions at the network scale that will be tested experimentally. Using these tools, the researchers aim to build cortex-like actomyosin networks that can dynamically morph into different organizations. The second aim is to determine how the mechanochemical properties of cortical actin networks can be tuned at the molecular scale to drive transitions between different force-generating actomyosin structures. This project aims to transform the current paradigm by showing that distinct actin networks, rather than being independently built, are mechanically integrated within the cortex and emerge via phase transitions.This collaborative US/France project is supported by the US National Science Foundation and the French Agence Nationale de la Recherche, where NSF funds the US investigator and ANR funds the partners in France.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.