CAREER: Mechanics of Vascular Smooth Muscle Cell Contraction - Subcellular Structure-Function Relationships

职业：血管平滑肌细胞收缩的力学 - 亚细胞结构-功能关系

• 批准号: 0846780
• 负责人: Nathan Sniadecki
• 金额: $ 40万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0846780&HistoricalAwards=false
• 关键词: CAREER; Mechanics; Vascular; Smooth; Muscle

The goal of this Faculty Early Career Development (CAREER) project is to (1) advance a conceptual framework for the mechanics of contraction in vascular smooth muscle (VSM) cells through nano-mechanical testing and computational modeling and (2) to create an educational program that incorporates nano-biomechanics and biomaterials with mechanical engineering learning. VSM cells form the middle layer in the walls of blood vessels and their contraction regulates vascular tone. The proposed experiments will characterize the structure-function relationships of the protein assemblies that form the contractile apparatus in VSM cells. The research will develop nano-biomechanical techniques that can measure the forces produced by the contractile apparatus under different loading conditions, external strains, and structural organization. The findings will be incorporated into a computational mechanochemical model based on first principles that ultimately arrives at the fundamental relationships. The outcomes from this research will improve the analysis and design of biomaterials and tissue-engineered constructs used in cardiovascular repair by determining their effect on VSM contraction. The transformative aspect of this proposal is a methodology for cell mechanics that considers the role of subcellular mechanical factors. This methodology will be general enough to be translated to other smooth muscle and nonmuscle cell types. This proposal will build a learning pathway between engineering and the biomedical disciplines through an integrated research and teaching approach that will enrich the curriculum at the University of Washington. The planned outreach efforts will attract underrepresented K-12 students to engineering by exposing them to the unique interfaces that exist between biology and engineering. To complement this outreach, a virtual organization focused on biology and engineering at the nanoscale will be established in order to integrate the research and education of this proposal and to promote collaborations in the field of nano-biomechanics.

这个教师早期职业发展（Career）项目的目标是：(1)通过纳米力学测试和计算建模来推进血管平滑肌（VSM）细胞收缩力学的概念框架；(2)创建一个将纳米生物力学和生物材料与机械工程学习相结合的教育计划。VSM细胞形成血管壁的中间层，其收缩调节血管张力。提出的实验将表征在VSM细胞中形成收缩装置的蛋白质组件的结构-功能关系。该研究将开发纳米生物力学技术，可以测量在不同负载条件下，外部应变和结构组织下收缩装置产生的力。这些发现将被纳入一个基于基本原理的计算力学化学模型，最终得出基本关系。本研究的结果将通过确定生物材料和组织工程结构对VSM收缩的影响，改善用于心血管修复的生物材料和组织工程结构的分析和设计。这一提议的变革方面是一个方法的细胞力学，考虑亚细胞力学因素的作用。这种方法将是通用的，足以转化为其他平滑肌和非肌肉细胞类型。该提案将通过综合研究和教学方法在工程和生物医学学科之间建立一条学习途径，这将丰富华盛顿大学的课程。计划中的拓展工作将通过向学生们展示存在于生物学和工程学之间的独特界面，吸引代表性不足的K-12学生学习工程学。为了补充这一扩展，将建立一个专注于纳米尺度生物和工程的虚拟组织，以整合本提案的研究和教育，并促进纳米生物力学领域的合作。