CAREER: Biomechanical Phenotyping of Contractile Vascular Smooth Muscle Cells

本CAREER提案的主要目标是研究血管平滑肌细胞的机械力介导的生物力学反应，平滑肌细胞是机械加重血管疾病的关键参与者。虽然已经有研究表征血管平滑肌细胞对机械刺激的细胞反应，但其反应的精确机械特性（包括其固有收缩和细胞刚度调节）在很大程度上仍然难以捉摸和未表征。鉴于血管平滑肌细胞的收缩和机械刚度调节在调节高血压诱导的血管病理中的关键作用，我们的研究旨在通过利用我们在微加工和细胞力学方面的专业知识，产生新的微机械工具来研究血管平滑肌细胞的力介导的生物力学表型变化，从而专门解决这一关键知识差距。高血压患者血管平滑肌细胞收缩和细胞刚度的生物力学变化在调节血管壁的适应和重塑中起着重要的功能作用。因此，更好地了解外力与血管平滑肌细胞生物力学特性变化之间的密切相互作用，将为血管平滑肌细胞如何转导这些力提供关键见解，并最终为开发特异性干扰压力诱导血管病变的药物铺平道路。作为职业发展计划的一个组成部分，将针对不同教育水平、性别和种族的学生制定一项全面的教育计划。在此CAREER提案的背景下开发的技术将被用作针对安娜堡和伊普斯兰蒂学区K-12学生的外展活动的工具。我们将开发旨在改变K-12学生对科学和工程的先入为主观念的教育模块。一个新的跨学科课程，生物力学也将开发作为这个职业建议的结果。

CBET-1149401FuThe major goal of this CAREER proposal is to investigate mechanical force-mediated biomechanical responses of vascular smooth muscle cells, a key player in the context of mechanically exacerbated vascular diseases. Although there have been studies characterizing cellular responses of vascular smooth muscle cells to mechanical stimuli, the precise mechanical characteristics of their responses (including their innate contraction and cell stiffness modulation) remains largely elusive and uncharacterized. Given the critical involvements of contraction and mechanical stiffness modulations of vascular smooth muscle cells in regulating hypertension-induced vascular pathologies, our research is set out to specifically address this critical knowledge gap by leveraging our demonstrated expertise in microfabrication and cell mechanics to generate novel micromechanical tools to investigate force-mediated biomechanical phenotypic changes of vascular smooth muscle cells. Biomechanical changes in vascular smooth muscle cell contraction and cell stiffness play an important functional role in regulating adaptation and remodeling of vessel walls in hypertension. Thus, a better understanding of the intimate interaction between external forces and changes in biomechanical properties of vascular smooth muscle cells will provide critical insights into how vascular smooth muscle cells transduce these forces and ultimately pave the way to developing drugs that specifically interfere with pressure-induced vascular pathologies. As an integral part of this CAREER proposal, a comprehensive education plan will be developed to target students from different educational levels and genders and ethnicities. Technologies developed in the context of this CAREER proposal will be used as vehicles for outreach activities targeting K-12 students in Ann Arbor and Ypsilanti school districts. We will develop educational modules aimed at altering preconceptions of science and engineering held by K-12 students. A new interdisciplinary course in Biomechanics will also be developed as an outcome of this CAREER proposal.