title: Interactions between connected half-sarcomeres produce emergent mechanical behavior in a mathematical model of muscle.
abstract: Most reductionist theories of muscle attribute a fiber's mechanical properties to the scaled behavior of a single half-sarcomere. Mathematical models of this type can explain many of the known mechanical properties of muscle but have to incorporate a passive mechanical component that becomes approximately 300% stiffer in activating conditions to reproduce the force response elicited by stretching a fast mammalian muscle fiber. The available experimental data suggests that titin filaments, which are the mostly likely source of the passive component, become at most approximately 30% stiffer in saturating Ca2+ solutions. The work described in this manuscript used computer modeling to test an alternative systems theory that attributes the stretch response of a mammalian fiber to the composite behavior of a collection of half-sarcomeres. The principal finding was that the stretch response of a chemically permeabilized rabbit psoas fiber could be reproduced with a framework consisting of 300 half-sarcomeres arranged in 6 parallel myofibrils without requiring titin filaments to stiffen in activating solutions. Ablation of inter-myofibrillar links in the computer simulations lowered isometric force values and lowered energy absorption during a stretch. This computed behavior mimics effects previously observed in experiments using muscles from desmin-deficient mice in which the connections between Z-disks in adjacent myofibrils are presumably compromised. The current simulations suggest that muscle fibers exhibit emergent properties that reflect interactions between half-sarcomeres and are not properties of a single half-sarcomere in isolation. It is therefore likely that full quantitative understanding of a fiber's mechanical properties requires detailed analysis of a complete fiber system and cannot be achieved by focusing solely on the properties of a single half-sarcomere.
authors.affiliation: Department of Physiology and Center for Muscle Biology, University of Kentucky, Lexington, Kentucky, USA. k.s.campbell@uky.edu
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Campbell
mesh_terms: D000199:Actins / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology*; D003198:Computer Simulation; D016014:Linear Models; D008954:Models, Biological; D009210:Myofibrils / Q000502:physiology; D009218:Myosins / Q000502:physiology; D017711:Nonlinear Dynamics; D016658:Psoas Muscles / Q000502:physiology*; D011817:Rabbits; D012518:Sarcomeres / Q000502:physiology*; D013314:Stress, Mechanical; D049490:Systems Biology / Q000379:methods*
chemical_list: D000199:Actins; D009218:Myosins