CAREER: Micro and Nano Methods to Reveal Cell Sensitivities to Local Stiffness

职业：揭示细胞对局部硬度敏感性的微纳米方法“该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。“将开发一类三维微力传感器和一类集成微力传感器的基底，以测量细胞对局部刚度的敏感性;将开发一类具有微米和纳米尺度刚度图案的连续基底，以研究细胞对局部基底刚度（SS）的敏感性;将开发一类具有磁流变和磁流体的基底，以研究细胞对变化的SS的响应;基于所获得的实验结果，将在分子水平上建立一个详细的生物物理模型来描述细胞对SS的动态力学敏感机制和过程。智力优势：已经发现细胞粘附、铺展、迁移和分化对细胞生长的基底的硬度极其敏感。 但细胞局部感知SS的机制以及细胞如何整合局部SS信息并将其转化为生物学行为仍不清楚，这是本研究的动机和问题。 该项目的成功完成将大大提高我们对细胞机械敏感性和机械转导，组织中的细胞行为和组织发育的理解。 与广泛使用的表面形貌和化学图案化一样，本项目中引入的基底刚度的微米和纳米图案化概念开辟了一种新的范式，并对细胞和组织机械生物学和工程及其应用的研究具有变革性。更广泛的影响：从拟议的研究中得出的结果为我们实现细胞和组织发育的微机械控制提供了基础知识，这在组织工程和再生医学中具有重要的应用。 所开发的微米和纳米方法可以用于或扩展到任何其他研究，包括机械性能和相互作用的测量，界面现象的检查，以及图案化表面的制造。 该教育计划将促进科学和工程中代表性不足的群体的参与，迅速向广大受众传播研究进展，为佛罗里达理工学院新的生物医学工程研究生课程提供一些核心课程和设施，并促进跨学科的研究和教育。 讲座和示范将在公共场所举行;夏令营和短期培训课程将组织和大量的座位将保留给学生从代表性不足的群体，三个新的研究生课程将提供在佛罗里达技术;一个非正式的俱乐部命名？更紧密的互动？将为来自佛罗里达理工学院工程和生物系的学生、教师和工作人员建立。

CAREER: Micro and Nano Methods to Reveal Cell Sensitivities to Local Stiffness"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."A class of three-dimensional micro force sensors and a class of substrates with integrated micro force sensors will be developed to measure the cell sensitivities to local stiffness; A class of continuous substrates with stiffness patterns at micro- and nano-meter scales will be developed to study cell sensitivities to local substrate stiffness (SS); A class of substrates with magnetorheological and magnetic fluids will be developed to study cell response to changing SS; Based on the obtained experimental results, a detailed biophysical model will be established at the molecular level to describe the dynamic cell mechanosensitive mechanism and process to SS. Intellectual Merit: Cell adhesion, spreading, migration, and differentiation have been found to be extremely sensitive to the stiffness of the substrates on which the cells were grown. But the mechanism through which the cells sense the SS locally and how the cells integrate the local SS information and transfer this information into biological behaviors remain largely unclear, which motivated and the issues will be addressed by this proposed research. The successful completion of this project will significantly enhance our understanding of cell mechanosensitivity and mechanotransduction, cell behaviors in tissues, and tissue development. Like the widely used patterning the surface topography and chemistry, the concept of micro- and nano-patterning the stiffness of the substrates, introduced in this project, opens a new paradigm and is transformative for the study of cell and tissue mechanobiology and engineering and its applications. Broader Impacts: The results to be drawn from the proposed research provide fundamental knowledge for us to realize micromechanical control of cell and tissue development, which has crucial applications in tissue engineering and regenerative medicine. The developed micro and nano methods can be used in or extended to any other studies involving measurements of mechanical properties and interactions, examinations of interfacial phenomena, and fabrications of patterned surfaces. The educational plan will promote the participation of underrepresented groups in science and engineering, quickly disseminate the research advances to broad audiences, result in some of the core curricula and facilities for the new Biomedical Engineering Graduate Program at Florida Tech, and boost cross-disciplinary research and education. Lectures and demonstrations will be given in public venues; Summer camps and short training courses will be organized and a significant number of seats will be reserved for students from underrepresented groups, and three new graduate courses will be offered at Florida Tech; An informal club named ?Closer Interaction? will be established for the students, faculty, and staff from the engineering and biological departments at Florida Tech.