title: Active shortening protects against stretch-induced force deficits in human skeletal muscle.
abstract: Skeletal muscle contraction results from molecular interactions of myosin "crossbridges" with adjacent actin filament binding sites. The binding of myosin to actin can be "weak" or "strong," and only strong binding states contribute to force production. During active shortening, the number of strongly bound crossbridges declines with increasing shortening velocity. Forcibly stretching a muscle that is actively shortening at high velocity results in no apparent negative consequences, whereas stretch of an isometrically (fixed-length) contracting muscle causes ultrastructural damage and a decline in force-generating capability. Our working hypothesis is that stretch-induced damage is uniquely attributable to the population of crossbridges that are strongly bound. We tested the hypothesis that stretch-induced force deficits decline as the prevailing shortening velocity is increased. Experiments were performed on permeabilized segments of individual skeletal muscle fibers obtained from human subjects. Fibers were maximally activated and allowed either to generate maximum isometric force (Fo), or to shorten at velocities that resulted in force maintenance of ≈50% Foor ≈2% FoFor each test condition, a rapid stretch equivalent to 0.1 × optimal fiber length was applied. Relative to prestretch Fo, force deficits resulting from stretches applied during force maintenance of 100, ≈50, and ≈2% Fowere 23.2 ± 8.6, 7.8 ± 4.2, and 0.3 ± 3.3%, respectively (means ± SD,n= 20). We conclude that stretch-induced damage declines with increasing shortening velocity, consistent with the working hypothesis that the fraction of strongly bound crossbridges is a causative factor in the susceptibility of skeletal muscle to stretch-induced damage.NEW & NOTEWORTHYForce deficits caused by stretch of contracting muscle are most severe when the stretch is applied during an isometric contraction, but prevented if the muscle is shortening at high velocity when the stretch occurs. This study indicates that velocity-controlled modulation of the number of strongly bound crossbridges is the basis for the observed relationship between stretch-induced muscle damage and prevailing shortening velocity.
authors.affiliation: Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, Michigan.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Anjali L
authors.initials: AL
authors.lastname: Saripalli
authors.affiliation: Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, Michigan.|Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan; and.|Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Kristoffer B
authors.initials: KB
authors.lastname: Sugg
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan; and.|Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Christopher L
authors.identifier: http://orcid.org/0000-0002-2384-0171
authors.initials: CL
authors.lastname: Mendias
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.|Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Susan V
authors.initials: SV
authors.lastname: Brooks
authors.affiliation: Department of Surgery, Section of Plastic Surgery, University of Michigan, Ann Arbor, Michigan; claflin@umich.edu.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Claflin
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D004548:Elasticity / Q000502:physiology*; D006801:Humans; D007537:Isometric Contraction / Q000502:physiology*; D008297:Male; D055595:Mechanical Phenomena; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009218:Myosins / Q000378:metabolism; D055815:Young Adult
chemical_list: D000199:Actins; D009218:Myosins
keywords: permeabilized single fibers; skeletal muscle; stretch-induced injury