title: Slowly cycling Rho kinase-dependent actomyosin cross-bridge "slippage" explains intrinsic high compliance of detrusor smooth muscle.
abstract: Biological soft tissues are viscoelastic because they display time-independent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+-containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as "slipping" cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically.
authors.affiliation: Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia; and.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Neal
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Jia B
authors.initials: JB
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Tanner
authors.initials: T
authors.lastname: Hurley
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Miner
authors.affiliation: Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia; and.
authors.forename: John E
authors.initials: JE
authors.lastname: Speich
authors.affiliation: Department of Surgery, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Klausner
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia; paul.ratz@vcuhealth.org.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Ratz
mesh_terms: D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D001696:Biomechanical Phenomena; D003187:Compliance; D008297:Male; D008954:Models, Biological; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000201:enzymology*; D011817:Rabbits; D015398:Signal Transduction; D013314:Stress, Mechanical; D013997:Time Factors; D001743:Urinary Bladder / Q000201:enzymology*; D014783:Viscosity; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000205:Actomyosin; D054460:rho-Associated Kinases
keywords: ROCK; biomechanics; bladder; blebbistatin; contraction; cytochalasin D