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

“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衬底，用于测量单元对局部刚度的灵敏度；将开发一类具有微纳米尺度刚度模式的连续衬底，以研究细胞对局部衬底刚度（SS）的敏感性；将开发一类具有磁流变和磁流体的底物来研究细胞对SS变化的反应；基于获得的实验结果，将在分子水平上建立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：细胞的粘附、扩散、迁移和分化对生长细胞的基质的刚度极为敏感。但是细胞感知局部SS的机制以及细胞如何整合局部SS信息并将这些信息转化为生物行为在很大程度上仍然不清楚，这是本研究的动机和问题。本课题的成功完成将大大提高我们对细胞力学敏感性和力学转导、细胞在组织中的行为和组织发育的理解。与广泛应用的表面形貌和化学图案化一样，本项目引入的微纳米基材刚度图案化概念，为细胞和组织力学生物学和工程学及其应用的研究开辟了一个新的范式，具有革命性意义。更广泛的影响：本研究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，在组织工程和再生医学中具有重要应用。所开发的微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，以及图案表面的制造。该教育计划将促进未被充分代表的群体参与科学和工程，迅速将研究进展传播给广泛的受众，为佛罗里达理工学院新的生物医学工程研究生项目提供一些核心课程和设施，并促进跨学科研究和教育。在公共场所进行讲座和示范；将组织夏令营和短期培训课程，并为来自代表性不足群体的学生保留大量席位，佛罗里达理工学院将开设三门新的研究生课程；一个非正式的俱乐部叫？互动吗?将为佛罗里达理工学院工程系和生物系的学生、教师和工作人员设立。

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.