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

这个项目的基本目标是揭示控制细胞肌动蛋白皮质组装和组织的分子机制。肌动蛋白皮质是由肌动蛋白细丝和肌球蛋白马达连接到细胞膜上的一个薄网络，其结构和组织调控着细胞在迁移、分裂和形态发生过程中的形状变化。虽然大脑皮层的关键分子成分已经确定，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来了解皮质组装的多尺度动力学，这将使研究细胞生物学、生物物理学和机械生物学的研究人员受益。这一合作将在多学科和刺激的环境中为博士后和学生提供最先进的模拟和实验技术培训，他们将在那里合作和发展国际专业网络。从这个项目中学到的经验教训将被整合到PI开发的研究生和本科生的生物物理学课程中，以演示如何从分子组件之间的相互作用中产生自组织的生物系统。这个项目旨在开发新的实验方法来操纵重组的肌动蛋白网络中的组装、周转和力的产生。与此同时，研究人员将为大脑皮层建立一个多尺度模型，整合分子尺度的数据，生成网络尺度的预测，并进行实验测试。使用这些工具，研究人员的目标是建立皮质样的肌动球蛋白网络，可以动态地变形为不同的组织。第二个目标是确定如何在分子水平上调节皮质肌动蛋白网络的机械力化学性质，以驱动不同产生力量的肌球蛋白结构之间的转变。这个项目旨在通过展示不同的肌动蛋白网络，而不是独立构建的，机械地整合在大脑皮层内，并通过相变而出现。这个美法合作项目得到了美国国家科学基金会和法国国家科学基金会的支持，其中NSF资助美国的研究人员，ANR资助法国的合作伙伴。这个奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.