西亚试剂:Fluidization and Resolidification of the Human Bladder Smoo
发布时间:2025-06-23
Fluidization and Resolidification of the Human Bladder Smooth Muscle Cell in Response to Transient Stretch
Cheng Chen1,2#, Ramaswamy Krishnan2#, Enhua Zhou2, Aruna Ramachandran3, Dhananjay Tambe2, Kavitha Rajendran2, Rosalyn M. Adam3, Linhong Deng1,2*, Jeffrey J. Fredberg2
1 Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing, China, 2 Program in Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America, 3 Urological Diseases Research Center, Department of Urology, Children's Hospital Boston and Department of Surgery, Harvard Medical School, Boston, Massachusetts, United States of America
Abstract
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 5min, 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.
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