Heart valve cell and matrix biomechanics and mechanobiology

心脏瓣膜疾病是加拿大心脏病最常见的原因之一。目前，没有药物可用于治疗瓣膜疾病。这是因为人们对引发和驱动这种疾病的细胞和分子知之甚少。重要的是，瓣膜在受到特定机械力的区域发生病变，这表明机械力导致这些区域局部的细胞从健康变为病变。为了研究这是如何发生的（因此希望确定治疗目标），我们需要更深入地了解整个瓣膜水平的力如何转移到瓣膜组织内的细胞以调节其功能。 本研究的目标是开发和使用基于计算机的模拟和实验研究，以：（a）测量健康和患病瓣膜组织的微尺度机械特性;（B）确定应变如何从瓣膜传递到细胞再到细胞内的细胞骨架，以及应变传递是否在疾病中改变或在瓣膜的不同区域中不同;以及（c）确定瓣膜组织硬度是否影响细胞对外部机械力的响应。这些研究将更好地定义瓣膜细胞在正常和病理功能期间感受到的局部机械刺激。这些信息将立即转化为生物学研究的设计模型，这些模型比目前使用的系统更能代表实际瓣膜。此外，这些研究将通过提供有关生物材料与瓣膜细胞在典型机械载荷下相互作用的关键信息，帮助设计工程化置换瓣膜组织。在这些项目中工作的学员将获得广泛的跨学科专业知识，这些技术可以转移到其他研究领域和行业，使他们对生物技术和生物医学工程的职业需求很高。

Diseases of the heart valves are among the most frequent causes of heart disease in Canada. Currently, there is no medicine available to treat valve disease. This is because little is known about the cells and molecules that initiate and drive the disease. Importantly, valves become diseased in regions subjected to specific mechanical forces, suggesting that mechanical forces cause the cells locally in these regions to change from healthy to diseased. In order to study how this occurs (and therefore hopefully identify therapeutic targets), we required a deeper understanding of how forces at the level of the whole valve get transferred to the cells within the valve tissue to regulate their function. The goal of this research is to develop and use computer-based simulations and experimental studies to: (a) measure the microscale mechanical properties of healthy and diseased valve tissue; (b) determine how strain is transferred from the valve to the cells to the cytoskeleton within the cell, and if strain transfer is altered in disease or is different in different regions of the valve; and (c) determine if valve tissue stiffness influences a cell's response to external mechanical forces. Together these studies will better define the local mechanical stimuli that valve cells feel during normal and pathological functioning. This information will be translated immediately to design models for biological studies that better represent the actual valve than the systems used currently. Additionally, these studies will aid in the design of engineered replacement valve tissues by providing critical information about the interaction between biomaterials and valve cells under typical mechanical loads. Trainees who work on these projects will gain broad interdisciplinary expertise in a variety of techniques that are transferable to other research areas and industries, making them in high demand for careers in biotechnology and biomedical engineering.