Probing Cellular Dynamic Mechanobiology Using Human Cardiomyocytes on a Stimuli-Responsive Nano-Topographic Substrate

这笔赠款将支持多学科研究，这将使新的方法在动态细胞机械生物学和智能生物材料。传统上，细胞机械生物学研究使用静态培养系统。 虽然这些系统很有用，但它们对细胞如何响应动态变化的微环境（如体内微环境）知之甚少。该项目旨在开发体外模型和方法，其中包括对细胞的时间依赖性机械结构线索。这些物理线索对于调节细胞形态（形状），分化（细胞变成什么）以及组织发育或愈合的每个阶段的功能都很重要。通过该项目获得的知识将在发育细胞生物学和心脏病理生理学相关的科学领域产生广泛的影响和各种应用。该项目还旨在将研究、教育和多样性结合起来，重点是加强不同教育层次的研究接触和机会。该项目的教育部分旨在帮助提高高中生和本科生对生物医学工程中跨学科，新兴和社会引人注目的方向的认识和熟悉程度。本研究的目标是使用体外形状记忆聚合物（SMP）平台来研究动态拓扑结构线索如何影响细胞机械生物学，特别强调人类心肌细胞的粘着动力学。动态生物材料基质、hiPSC技术和基因组编辑的结合将为建立新的分析工具和体外模型系统提供巨大潜力，用于广泛研究动态细胞机械生物学中的时间依赖性机械结构线索。这个动态平台将使我们能够测试我们的假设，即细胞外地形的变化将决定不同的动态反应的周边局灶性粘连和肌节连接costameres的心肌细胞，从而重组肌原纤维结构和控制收缩功能。本计画旨在研究动态结构线索如何调控周边局灶性粘连（目标1）和心脏特异性肌节相关的costameres（目标2），以及机械传导信号通路（FAK和雅普/TAZ）参与这些细胞发育过程（目标3）该奖项反映了NSF的法定使命，并通过使用基金会的智力价值进行评估，更广泛的影响审查标准。

This grant will support a multidisciplinary research that will enable new approaches in dynamic cell mechanobiology and smart biomaterials. Traditionally, cell mechanobiology is studied using static culture systems. Though useful, these systems provide little knowledge as to how the cells respond to a dynamic changing microenvironment, such as in the body. This project aims to develop in vitro models and approaches that include time-dependent mechano-structural cues to cells. These physical cues are important to regulating of cellular morphology (shape), differentiation (what cells become), and function at each phase of tissue development or healing. The knowledge gained through this project will have a broad impact and various applications in the scientific fields related to developmental cell biology and cardiac pathophysiology. This project is also designed to integrate research, education, and diversity with an emphasis on strengthening research exposure and opportunities at different education levels. The educational component of this project aims to help raise the awareness and familiarity of high-school students and undergraduate students with interdisciplinary, emerging and socially compelling directions within biomedical engineering. The goal of the present research is to use an in vitro shape-memory polymer (SMP) platform to investigate how dynamic topographic structural cues affect cellular mechanobiology, with a particular emphasis on the focal adhesion dynamics of human cardiomyocytes. The combination of dynamic biomaterial substrates, hiPSC technology and genome editing will provide a great potential to establish new analytical tools and in vitro model systems for broadly studying time-dependent mechano-structural cues in dynamic cell mechanobiology. This dynamic platform will allow us to test our hypothesis that extracellular topographic changes will dictate the different dynamic responses of both periphery focal adhesions and sarcomere-linked costameres of cardiomyocytes, thereby reorganizing myofibril structures and controlling contractile functions. This project aims to study how dynamic structural cues would regulate periphery focal adhesions (Objective 1) and cardiac-specific sarcomere-linked costameres (Objective 2), and how mechanotransduction signaling pathways (FAK and YAP/TAZ) are involved in these cellular developmental processes (Objective 3).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.