Mechanics Characterization of Cellular Force Regulation

描述(由申请人提供)： 这是盖伊·M·吉宁博士的职业发展奖申请的重新提交 与埃利奥特·L·埃尔森博士合作。Genin博士是华盛顿大学圣路易斯分校的机械工程学教授，他的目标是将自己的职业生涯转向定量生物学。埃尔森博士在吴大学领导着一个积极的研究项目，旨在开发可行的生物人造组织，并得到了美国国立卫生研究院的支持。为期5年的研究和培训计划的重点是发展应用固体力学概念来研究生物人工组织中细胞的主动力调节的专业知识。最初，杰宁博士计划进行密集的课程学习和正式的教学研究，并辅之以实验室工作。经过两年的学习，申请者计划在埃尔森博士的实验室里休假一年，合作研究理想化组织结构的机械特征。在最后两年，申请者将继续合作进行与宏观组织行为和微观细胞行为相关的研究。在研究和培训计划结束时，Genin博士将成为吴大学细胞和组织工程跨学科研究的主要合作伙伴，并得到美国国立卫生研究院的支持。该研究计划旨在量化理想化组织结构中细胞行为和组织行为之间的关系。这对于开发其机械性能模仿其所取代的健康组织的人造组织，以及确定体内细胞的机械反应至关重要。申请人开始这些研究的主要分析工具是改进的生物人造组织本构模型(目标1)。这项工作还需要仔细研究重塑的胶原蛋白(目标2.)申请人将继续研究更复杂的组织结构：首先是用心脏成纤维细胞填充的重组胶原(目标3)，然后是用心脏成纤维细胞和心肌细胞填充的类似组织(目标4)。

DESCRIPTION (provided by applicant): This is a resubmission of an application for a career development award for Dr. Guy M. Genin in collaboration with Dr. Elliot L Elson. Dr. Genin is a Mechanical Engineering professor at Washington University in St. Louis (WU) who aims to shift his career towards quantitative biology. Dr. Elson heads a vigorous research program at WU aimed at developing viable bioartificial tissues, and is supported by the NIH. The focus of the 5-year research and training program is developing expertise in applying solid mechanics concepts to study active force regulation by cells in bioartificial tissues. Initially, Dr. Genin plans an intensive program of coursework and formal didactic study, coupled with laboratory work. After two years of study, the applicant plans a sabbatical year in Dr. Elson's lab, collaborating on mechanical characterization of idealized tissue constructs. In the final two years, the applicant would continue to collaborate on studies relating macroscopic tissue behavior and microscopic cellular behavior. By the end of the research and training plan, Dr. Genin would be situated to become a leading partner in interdisciplinary studies of cell and tissue engineering at WU, and supported by the NIH. The research plan aims to quantify the relationship between cellular behavior and tissue behavior in idealized tissue constructs. This is vital for developing artificial tissues whose mechanical properties mimic those of the healthy tissues they replace, and for determining the mechanical response of cells in vivo. The primary analytical tool with which the applicant will begin these studies is an improved constitutive model for bioartificial tissues (Aim 1). The work will also require careful study of remodeled collagen (Aim 2.) The applicant will proceed to study progressively more complicated tissue constructs: first, reconstituted collagen populated with cardiac fibroblasts (Aim 3), and then a similar tissue populated with cardiac fibroblasts and cardiomyocytes (Aim 4.)