Abstract
Using stress sensitive FRET sensors we have measured cytoskeletal stresses in α-actinin and the associated reorganization of the actin cytoskeleton in cells subjected to chronic shear stress. We show that long-term shear stress reduces the average actinin stress and this effect is reversible with removal of flow. The flow-induced changes in cytoskeletal stresses are found to be dynamic, involving a transient decrease in stress (phase-I), a short-term increase (3–6 min) (Phase-II), followed by a longer-term decrease that reaches a minimum in ∼20 min (Phase-III), before saturating. These changes are accompanied by reorganization of the actin cytoskeleton from parallel F-actin bundles to peripheral bundles. Blocking mechanosensitive ion channels (MSCs) with Gd3+ and GsMTx4 (a specific inhibitor) eliminated the changes in cytoskeletal stress and the corresponding actin reorganization, indicating that Ca2+ permeable MSCs participate in the signaling cascades. This study shows that shear stress induced cell adaptation is mediated via MSCs.
Highlights
Renal epithelial cells experience a wide range of shear stress due to urinary flow
Our study reveals that long-term (,3 hrs) exposure to fluid shear stress produces three distinct phases of cytoskeletal stress variation, each lasting for minutes
Colocalization is shown by expressing actininsstFRET in Madin Darbey Canine Kidney (MDCK) cells (Fig. 1b) and subsequently staining actin with phalloidin-Alexa Fluor 568 (Fig. 1c)
Summary
Renal epithelial cells experience a wide range of shear stress due to urinary flow. Through various adaptation mechanisms cells adjust their cytoskeleton structure, adhesion assembly and cell-cell interactions, thereby accommodating the mechanical challenge [1,2]. This remodeling minimizes local stresses and affects membrane transport and other cell functions [3,4]. Exposure of renal tubule cells to chronic flow results in reorganization of the cytoskeleton and an increase in the formation of cell-cell junctions [5,6]. These, in turn, can activate biochemical pathways that affect cell morphology, migration and growth [8,9,10]
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