Ultrastructural and mechanical changes in tubular epithelial cells by angiotensin II and aldosterone as observed with...

Tubular epithelial cells (TECs) play an important pathophysiological role in the promotion of renal fibrosis. Quantitative analysis of the mechanical changes in TECs may be helpful in evaluating novel pharmacological strategies. Atomic force microscopy (AFM) is a common nanotechnology tool used for imaging and measuring interaction forces in biological systems. In this study, we used AFM to study ultrastructural and mechanical changes in TECs mediated by the renin-angiotensin-aldosterone system. We quantitatively analyzed changes in the mechanical properties of TECs using three extrinsic factors, namely, chemical fixation, angiotensin II (AT II), and aldosterone (AD). Fixed TECs were 11 times stiffer at the cell body and 3 times stiffer at the cell-cell junction compared to live TECs. After stimulation with AT II, live TECs were four times stiffer at the junctional area than at the cell body, while fixed TECs after AT II stimulation were approximately two times stiffer at the both cell body and cell-cell junction compared to fixed unstimulated TECs. Fixed TECs also reflected changes in the mechanical properties of TECs at the cell body region after AD stimulation. Together, our results suggest that cell stiffness at the cell body region may serve as an effective index for evaluating drugs and stimulation, regardless of whether the cells are live or fixed at the time of analysis. In addition, studying the changes to the intrinsic mechanical property of TECs after application of external stimuli may be useful for investigating pathophysiologic mechanisms and effective therapeutic strategies for renal injury.