Proposed role of the M-band in sarcomere mechanics and mechano-sensing: a model study.
In sarcomeres of striated muscles the middle parts of adjacent thick filaments are connected to each other by the M-band proteins. To understand the role of the M-band in sarcomere mechanics a model of forces which pull a thick filament to opposite Z-disks of a sarcomere is considered. Forces of actin-myosin cross-bridges, I-band titin segments and the M-band are accounted for. A continual expression for the M-band force is obtained assuming that the M-band proteins which connect neighbor thick filaments have nonlinear elastic properties. On the ascending and descending limbs of the force-length diagram cross-bridge forces tend to destabilize sarcomere while titin tries to restore its symmetric configuration. When destabilizing cross-bridge force exceeds a critical limit, symmetric configuration of a sarcomere becomes unstable and the M-band buckles. Stiffness of the M-band increases stability only if the M-band is anchored to the extra-sarcomere cytoskeleton. Realistic magnitudes of the M-band buckling require that the M-band proteins have essentially nonlinear elasticity. The buckling may explain the M-band bending and axial misalignment of the thick filaments observed in contracting muscle. We hypothesize that the buckling stretches the titin protein kinase domain localized in the M-band being the signal for mechanical control of gene expression and protein turnover in striated muscle.
Shabarchin
A A
AA
Department of Biomechanics, Institute of Mechanics, M.V. Lomonosov Moscow University, 1 Mitchurinsky prosp., 119992 Moscow, Russia.
Tsaturyan
Andrey K
AK
D000818:Animals; D003198:Computer Simulation; D055119:Elastic Modulus / Q000502:physiology; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology*; D013314:Stress, Mechanical
D009124:Muscle Proteins