title: Disassembly of myofibrils and potential imbalanced forces on Z-discs in cultured adult cardiomyocytes.
abstract: Myofibrils are the main protein structures that generate force in the beating heart. Myofibril disassembly is related to many physiological and pathological processes. This study investigated, in a cultured rat adult cardiomyocyte model, the effect of force imbalance on myofibril disassembly. The imbalance of forces that were exerted on Z-discs was induced by the synergistic effect of broken intercalated discs and actin-myosin interaction. Cardiomyocytes with well-preserved intercalated discs were isolated from adult rat ventricles. The ultrastructure of cardiomyocyte was observed using a customized two-photon excitation fluorescence and second harmonic generation imaging system. The contraction of cardiomyocytes was recorded with a high-speed CCD camera, and the movement of cellular components was analyzed using a contractile imaging assay technique. The cardiomyocyte dynamic remodeling process was recorded using a time-lapse imaging system. The role of actin-myosin interaction in myofibril disassembly was investigated by incubating cardiomyocytes with blebbistatin (25 μM). Results demonstrated that the hierarchical disassembly process of myofibrils was initiated from cardiomyocyte free ends where intercalated discs had broken, during which the desmin network near the free cell ends was destroyed to release single myofibrils. Analysis of force (based on a schematic model of cardiomyocytes connected at intercalated discs) suggests that breaking of intercalated discs caused force imbalance on both sides of the Z-discs adjacent to the cell ends due to actin-myosin interaction. The damaged intercalated discs and actin-myosin interaction induced force imbalance on both sides of the Z-discs, which played an important role in the hierarchical disassembly of myofibrils. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267.
authors.forename: Honghai
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Bioengineering and COMSET, Clemson University, Clemson, South Carolina, 29634.
authors.forename: Wan
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Bioengineering and COMSET, Clemson University, Clemson, South Carolina, 29634.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267.
authors.forename: Jingcai
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, 29425.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Borg
authors.affiliation: Department of Bioengineering and COMSET, Clemson University, Clemson, South Carolina, 29634.
authors.forename: Bruce Z
authors.initials: BZ
authors.lastname: Gao
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, 45267.
authors.forename: Meifeng
authors.initials: M
authors.lastname: Xu
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D008954:Models, Biological; D009210:Myofibrils / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000199:Actins; D006576:Heterocyclic Compounds, 4 or More Rings; C472645:blebbistatin; D009218:Myosins
keywords: Z-disc; cardiomyocyte; disassembly of myofibrils; imbalanced force; intercalated disc