Quantifying cellular mechanics and adhesion in renal tubular injury using single cell force spectroscopy

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• 作者：Eleftherios Siamantouras ; PhD^a ; Claire E. Hills ; PhD^b ; Paul E. Squires ; PhD^b ; Kuo-Kang Liu ; PhD^a ; ^{I.K.Liu@warwick.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Atomic force microscopy ; TGF-β1 ; Fibrosis ; Nanomechanics ; Cell elasticity
• 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：12
• 期：4
• 页码：1013-1021
• 全文大小：997 K

文摘

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 predominantly focussed on the loss of cell surface molecular binding events that include altered protein ligation. In the current study, atomic 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 human proximal tubule (HK2). AFM indentation of TGF-β1 treated HK2 cells showed a significant increase (42%) in the elastic modulus (stiffness) compared to control. Fluorescence microscopy confirmed that increased cell stiffness is accompanied by reorganization of the cytoskeleton. The corresponding changes in stiffness, due to F-actin rearrangement, affected the work of detachment by changing the separation distance between two adherent cells. Overall, our novel data quantitatively demonstrate 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.