Fluidization and Resolidification of the Human Bladder Smooth Muscle Cell in Response to Transient Stretch
نویسندگان
چکیده
BACKGROUND Cells resident in certain hollow organs are subjected routinely to large transient stretches, including every adherent cell resident in lungs, heart, great vessels, gut, and bladder. We have shown recently that in response to a transient stretch the adherent eukaryotic cell promptly fluidizes and then gradually resolidifies, but mechanism is not yet understood. PRINCIPAL FINDINGS In the isolated human bladder smooth muscle cell, here we applied a 10% transient stretch while measuring cell traction forces, elastic modulus, F-actin imaging and the F-actin/G-actin ratio. Immediately after a transient stretch, F-actin levels and cell stiffness were lower by about 50%, and traction forces were lower by about 70%, both indicative of prompt fluidization. Within 5 min, F-actin levels recovered completely, cell stiffness recovered by about 90%, and traction forces recovered by about 60%, all indicative of resolidification. The extent of the fluidization response was uninfluenced by a variety of signaling inhibitors, and, surprisingly, was localized to the unstretch phase of the stretch-unstretch maneuver in a manner suggestive of cytoskeletal catch bonds. When we applied an "unstretch-restretch" (transient compression), rather than a "stretch-unstretch" (transient stretch), the cell did not fluidize and the actin network did not depolymerize. CONCLUSIONS Taken together, these results implicate extremely rapid actin disassembly in the fluidization response, and slow actin reassembly in the resolidification response. In the bladder smooth muscle cell, the fluidization response to transient stretch occurs not through signaling pathways, but rather through release of increased tensile forces that drive acute disassociation of actin.
منابع مشابه
A biomechanical model for fluidization of cells under dynamic strain.
Recent experiments have investigated the response of smooth muscle cells to transient stretch-compress (SC) and compress-stretch (CS) maneuvers. The results indicate that the transient SC maneuver causes a sudden fluidization of the cell while the CS maneuver does not. To understand this asymmetric behavior, we have built a biomechanical model to probe the response of stress fibers to the two m...
متن کاملMechanical stretch regulates cell survival in human bladder smooth muscle cells in vitro.
Our understanding of the pathophysiology of the overactive bladder is poor. It has been proposed that localized contractions result in the abnormal stretching of bladder smooth muscle. We hypothesize that stretch regulates the cellular processes that determine tissue size. The purpose of this study was to investigate the effect of stretch on apoptosis, proliferation, cell hypertrophy, and growt...
متن کاملRegulation of Cyr61 gene expression by mechanical stretch through multiple signaling pathways.
The cysteine-rich protein 61 (Cyr61) is a signaling molecule with functions in cell migration, adhesion, and proliferation. This protein is encoded by an immediate early gene whose expression is mainly induced by serum growth factors. Here we show that Cyr61 mRNA levels increase sharply in response to cyclic mechanical stretch applied to cultured bladder smooth muscle cells. Stretch-induced cha...
متن کاملObstruction stimulates COX-2 expression in bladder smooth muscle cells via increased mechanical stretch.
Studies were performed to investigate the regulatory mechanism of bladder cyclooxygenase-2 (COX-2) expression after outlet obstruction. In situ hybridization of murine bladder tissues using COX-2-specific riboprobes demonstrated that COX-2 expression was induced predominantly in the bladder smooth muscle cells after outlet obstruction. To study the effect of increased mechanical stretch on COX ...
متن کاملCyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells.
Cyclic mechanical stretch of bladder smooth muscle cells (SMC) increases rates of DNA synthesis and stimulates transcription of the gene for heparin-binding epidermal growth factor-like growth factor (HB-EGF), an ErbB1/EGF receptor ligand that has been linked to hypertrophic bladder growth. In this study we sought to clarify the signaling pathways responsible for mechanotransduction of the stre...
متن کامل