Abstract
BackgroundCells 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 FindingsIn 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.ConclusionsTaken 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.
Highlights
Cells in vivo are routinely subjected to mechanical stimuli that markedly influence their structure and function [1,2,3,4,5]
The primary goal of this study is to investigate in the human bladder smooth muscle (HBSM) cell the structural and molecular level changes that underlie the fluidization response
Changes of traction force The traction force is the net force per unit area transmitted from the adherent cell to the substrate, and must be balanced by the internal stress in the cell body [23]
Summary
Cells in vivo are routinely subjected to mechanical stimuli that markedly influence their structure and function [1,2,3,4,5]. We have shown recently that in response to a transient stretch-unstretch maneuver, cells across a wide range of physiological systems including airway, kidney, and blood vessels, respond by promptly ablating their stiffness and cell traction forces, while transiently increasing their loss tangent [6,7]. Taken together, these mechanical responses demonstrate that the cell acutely fluidizes [7]. To investigate specificity of the fluidization response, we pretreated HBSM cells with a panel of signaling inhibitors whose effects on bladder smooth muscle cell physiology are well known [13,14,15]. We have shown recently that in response to a transient stretch the adherent eukaryotic cell promptly fluidizes and gradually resolidifies, but mechanism is not yet understood
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