CAREER: Microscale Mechanobiology of Actomyosin Stress Fiber Bundles: An Integrated Program for Research and Education in Cellular Bioengineering

该学院早期职业发展(Career)计划奖项的目标是使用生物光子学、遗传学和计算工具的组合来研究肌动球蛋白应激纤维的机制以及控制这些特性的潜在信号机制。应力纤维是一种微米级、可收缩的结构电缆，它横跨活细胞，使细胞能够产生对周围环境的牵引力，这一过程对组织结构的移动和维护至关重要。根据该奖项进行的研究将应用分子生物学工具来操纵应激纤维中特定分子的浓度和活性，并使用激光纳米外科和相关的微技术来研究这些分子对应激纤维功能的贡献。同时，将开发一个多尺度计算模型，将这些分子组分的活动与应力纤维力学和整体细胞机械生物学特性联系起来。如果成功，这些研究将大大增加该领域对细胞骨架收缩能力的分子调控的理解，并代表着实验和计算的紧密结合。从这些努力中获得的知识还将通过揭示细胞结构和力学的“设计原则”来增强该领域操纵细胞和组织结构和功能的能力。这反过来可能有助于推动组织工程、再生医学和其他生物界面技术系统的演变。该教育计划侧重于本科生和研究生阶段的细胞生物工程课程开发，以及在获奖者所在机构与两个非博士生物工程项目之间建立合作伙伴关系，以开发学士和MS级别的课程。这两项倡议将涉及广泛分享课程材料，并讨论如何有效地将细胞生物工程概念纳入本科生和专业前培训。

The objective of this Faculty Early Career Development (CAREER) Program award is to use a combination of biophotonic, genetic, and computational tools to investigate the mechanics of actomyosin stress fibers and the underlying signaling mechanisms that control these properties. Stress fibers are micrometer-scale, contractile structural cables that traverse across living cells and enable cells to generate tractional forces against their surroundings, a process critical to locomotion and maintenance of tissue architecture. Studies conducted under this award will apply molecular biological tools to manipulate the concentrations and activities of specific molecules within stress fibers and use laser nanosurgery and related microtechnologies to investigate the contributions of these molecules to stress fiber function. In parallel, a multi-scale computational model will be developed to relate the activities of these molecular components to stress fiber mechanics and overall cellular mechanobiological properties. If successful, these studies would add significantly to the field's understanding of the molecular regulation of cytoskeletal contractility and represent a tight integration of experiment and computation. The knowledge gained from these efforts will also enhance the field's ability to manipulate cell and tissue structure and function by revealing "design principles" for cell structure and mechanics. This in turn may help drive the evolution of systems for tissue engineering, regenerative medicine, and other bio-interfacial technologies. The educational plan focuses on course development in cellular bioengineering at the undergraduate and graduate level as well as the creation of partnerships between the awardee's institution and two non-PhD-focused bioengineering programs for BS- and MS-level curriculum development. Both initiatives will involve extensive sharing of course material and discussions of how to effectively incorporate cellular bioengineering concepts into undergraduate and pre-professional training.