Measuring the influence of biomechanical forces on biological processes.

暴露于生物力学力（如张力、剪切应力和搏动血流动力学应变）对心血管系统的正常发育至关重要，力传递的改变可导致包括肾脏和心脏疾病在内的病理后果。物理力转化为生物反应的现象被称为机械转导，这是通过驱动基因和蛋白质表达变化的生化信号来调节的。为了更好地理解受机械转导影响的分子和细胞信号，有必要使用相对简单的实验模型，如单细胞培养。例如，为了研究压力增加如何影响心脏的硬度，研究心脏成纤维细胞是合乎逻辑的，因为这些细胞控制着心脏中胶原蛋白的水平。同样，为了评估血压和血液过滤的变化如何影响肾功能，可以研究肾脏中被称为足细胞的独特过滤细胞。虽然在静态培养中培养这些独特的细胞类型已经取得了显著的进步，但这些条件并没有提供在完整器官中看到的额外的生物力学挑战。Flexcell FX6000张力系统是一种专门的细胞拉伸设备，能够在简化的体外细胞培养模型中模拟复杂的体内生物力学力。这是市场上唯一一种可以控制培养细胞多向拉伸的仪器，模拟血管和血管化组织的气球状扩张。所要求的设备将推进圭尔夫大学真核细胞信号传导（Jones）和心脏生理学（Gillis）的两个前沿研究项目，也将被校园内心血管科学、癌症生物学和神经科学的大量多学科研究人员使用。共同申请者要求Flexcell系统解决以下突出的研究问题：1)生物力学力如何影响足细胞的粘附特性？2)由特定基因突变引起的细胞信号模式改变是如何导致足细胞丢失的？3)生物力学力在刺激神经元和癌细胞迁移中的作用是什么？4)血压变化如何导致胶原沉积增加和心脏纤维化？5)逆转鳟鱼心脏纤维化的细胞通路是什么？解决这些问题将为了解生物力学力在驱动复杂生物组织正常发育中的作用以及力传递的改变如何导致组织功能障碍提供基本的见解。

Exposure to biomechanical forces (such as tension, shear stress and pulsatile hemodynamic strain) is essential for normal development of the cardiovascular system, and alterations in force transmission can lead to pathological consequences including kidney and heart disease. The phenomenon by which physical forces are translated into biological responses is called mechanotransduction, and this is regulated via biochemical cues that drive changes in gene and protein expression. To better understand the molecular and cellular signals that are influenced by mechanotransduction, it is necessary to use relatively simple experimental models such as cultures of single cell types. For example, to investigate how an increase in pressure can influence the stiffness of the heart, it is logical to study cardiac fibroblasts as these cells control the level of collagen in the heart. Similarly, to assess how changes in blood pressure and blood filtration influence kidney function, the unique filtering cells of the kidney known as podocytes can be studied. While remarkable strides have been made in growing these unique cell types in static culture, these conditions do not provide the added biomechanical challenge seen in intact organs. The Flexcell FX6000 Tension System requested in this RTI application is a specialized cell stretch apparatus capable of simulating complex in vivo biomechanical forces in simplified in vitro cell culture models. It is the only instrument on the market that allows for controlled multidirectional stretch of cultured cells, mimicking the balloon-like expansion of blood vessels and vascularized tissues. The requested equipment will advance two leading edge research programs at the University of Guelph in eukaryotic cell signalling (Jones) and cardiac physiology (Gillis), and will also be used by a large group of multidisciplinary researchers in cardiovascular science, cancer biology as well as neuroscience on campus. The co-applicants require the Flexcell system to address the following outstanding research questions: 1) How do biomechanical forces influence the adhesive properties of podocytes? 2) How do changes in cell signalling patterns caused by specific genetic mutations lead to podocyte loss? 3) What is the role of biomechanical force is stimulating the migration of neurons and cancer cells? 4) How does a change in blood pressure lead to increased collagen deposition and cardiac fibrosis? 5) What are the cellular pathways involved in reversing cardiac fibrosis in the trout heart? Addressing these questions will provide fundamental insight into the role of biomechanical forces in driving the normal development of complex biological tissues, and how alterations in force transmission lead to tissue dysfunction.