A multisegmental cross-bridge kinetics model of the myofibril.
Striated muscle is a mechanical system that develops force and generates power in serving vital activities in the body. Striated muscle is a complex biological system; a single mammalian muscle fibre contains up to hundred or even more myofibrils in parallel connected via an inter-myofibril filament network. In one single myofibril thousands of sarcomeres are lined up as a series of linear motors. We recently demonstrated that half-sarcomeres (hS) in a single myofibril operate non-uniformly. We outline a mathematical framework based on cross-bridge kinetics for the simulation of the force response and length change of individual hS in a myofibril. The model describes the muscle myofibril in contraction experiments under various conditions. The myofibril is modeled as a multisegmental mechanical system of hS models, which have active and viscoelastic properties. In the first approach, a two-state cross-bridge formalism relates the hS force to the chemical kinetics of ATP hydrolysis, as first described by Huxley [1957. Muscle structure and theories of contraction. Prog. Biophys. Mol. Biol. 7, 255-318]. Two possible types of biological variability are introduced and modeled. Numerical simulations of a myofibril composed of four to eight hS show a non-uniform hS length distribution and complex internal dynamics upon activation. We demonstrate that the steady-state approximation holds only in restricted time zones during activation. Simulations of myofibril contraction experiments that reproduce the classic steady-state force-length and force-velocity relationships, strictly constrained or "clamped" in either end-held isometric or isotonic contraction conditions, reveal a small but conspicuous effect of hS dynamics on force.
ETH Zurich, Institute for Biomechanics, 8093 Zurich, Switzerland.
Urs
U
Stoecker
Ivo A
IA
Telley
Edgar
E
Stüssi
Jachen
J
Denoth
D000205:Actomyosin / Q000502:physiology; D000818:Animals; D007537:Isometric Contraction / Q000502:physiology; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009210:Myofibrils / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology
D000205:Actomyosin