Tubulointerstitial fibrosis represents the
major underlying pathology of diabetic nephropathy where loss of cell-to-cell adhesion is a critical step. To date, research has predo
minantly focussed on the loss of cell surface
molecular binding events that include altered protein ligation. In the current study, ato
mic force
microscopy single cell force spectroscopy (AFM-SCFS) was used to quantify changes in cellular stiffness and cell adhesion in TGF-β1 treated kidney cells of the hu
man proxi
mal tubule (HK2). AFM indentation of TGF-β1 treated HK2 cells showed a significant increase (42%) in the elastic
modulus (stiffness) co
mpared to control. Fluorescence
microscopy confir
med that increased cell stiffness is acco
mpanied by reorganization of the cytoskeleton. The corresponding changes in stiffness, due to F-actin rearrange
ment, affected the work of detach
ment by changing the separation distance between two adherent cells. Overall, our novel data quantitatively de
monstrate a correlation between cellular elasticity, adhesion and early
morphologic/phenotypic changes associated with tubular injury.
From the Clinical Editor
Diabetes affects many patients worldwide. One of the long term problems is diabetic nephropathy. Here, the authors utilized atomic force microscopy single cell force spectroscopy (AFM- SCFS) to study cellular stiffness and cell adhesion after TGF1 treatment in human proximal tubule kidney cells. The findings would help further understand the overall disease mechanism in diabetic patients.
