Physics, Harvard University, Cambridge, Massachusetts, USA.
Am J Physiol Cell Physiol. 2011 Mar;300(3):C397-405. doi: 10.1152/ajpcell.00438.2010. Epub 2010 Dec 1.
The mechanical properties of tissues and cells including renal glomeruli are important determinants of their differentiated state, function, and responses to injury but are not well characterized or understood. Understanding glomerular mechanics is important for understanding renal diseases attributable to abnormal expression or assembly of structural proteins and abnormal hemodynamics. We use atomic force microscopy (AFM) and a new technique, capillary micromechanics, to measure the elastic properties of rat glomeruli. The Young's modulus of glomeruli was 2,500 Pa, and it was reduced to 1,100 Pa by cytochalasin and latunculin, and to 1,400 Pa by blebbistatin. Cytochalasin or latrunculin reduced the F/G actin ratios of glomeruli but did not disrupt their architecture. To assess glomerular biomechanics in disease, we measured the Young's moduli of glomeruli from two mouse models of primary glomerular disease, Col4a3(-/-) mice (Alport model) and Tg26(HIV/nl) mice (HIV-associated nephropathy model), at stages where glomerular injury was minimal by histopathology. Col4a3(-/-) mice express abnormal glomerular basement membrane proteins, and Tg26(HIV/nl) mouse podocytes have multiple abnormalities in morphology, adhesion, and cytoskeletal structure. In both models, the Young's modulus of the glomeruli was reduced by 30%. We find that glomeruli have specific and quantifiable biomechanical properties that are dependent on the state of the actin cytoskeleton and nonmuscle myosins. These properties may be altered early in disease and represent an important early component of disease. This increased deformability of glomeruli could directly contribute to disease by permitting increased distension with hemodynamic force or represent a mechanically inhospitable environment for glomerular cells.
组织和细胞的力学特性，包括肾肾小球，是它们分化状态、功能和对损伤反应的重要决定因素，但这些特性尚未得到很好的描述或理解。了解肾小球力学对于理解归因于结构蛋白异常表达或组装以及异常血液动力学的肾脏疾病非常重要。我们使用原子力显微镜（AFM）和一种新的技术，即毛细力学，来测量大鼠肾小球的弹性特性。肾小球的杨氏模量为 2500 Pa，用细胞松弛素和 latunculin 将其降低至 1100 Pa，用 blebbistatin 将其降低至 1400 Pa。细胞松弛素或 latunculin 降低了肾小球的 F/G 肌动蛋白比，但没有破坏其结构。为了评估疾病中的肾小球生物力学，我们测量了两种原发性肾小球疾病的小鼠模型，Col4a3(-/-) 小鼠（Alport 模型）和 Tg26(HIV/nl) 小鼠（HIV 相关性肾病模型）的肾小球杨氏模量，在组织病理学上肾小球损伤最小的阶段。Col4a3(-/-) 小鼠表达异常的肾小球基底膜蛋白，Tg26(HIV/nl) 小鼠足细胞在形态、粘附和细胞骨架结构方面有多种异常。在这两种模型中，肾小球的杨氏模量降低了 30%。我们发现肾小球具有特定的、可量化的生物力学特性，这些特性依赖于肌动蛋白细胞骨架和非肌肉肌球蛋白的状态。这些特性可能在疾病早期就发生了改变，是疾病的一个重要早期组成部分。肾小球的这种增加的可变形性可能通过允许在血液动力学力下增加膨胀而直接导致疾病，或者代表肾小球细胞的机械不适宜环境。
