Skeletal muscle resists stretch by rapid binding of the second motor domain of myosin to actin.
A shortening muscle is a machine that converts metabolic energy into mechanical work, but, when a muscle is stretched, it acts as a brake, generating a high resistive force at low metabolic cost. The braking action of muscle can be activated with remarkable speed, as when the leg extensor muscles rapidly decelerate the body at the end of a jump. Here we used time-resolved x-ray and mechanical measurements on isolated muscle cells to elucidate the molecular basis of muscle braking and its rapid control. We show that a stretch of only 5 nm between each overlapping set of myosin and actin filaments in a muscle sarcomere is sufficient to double the number of myosin motors attached to actin within a few milliseconds. Each myosin molecule has two motor domains, only one of which is attached to actin during shortening or activation at constant length. A stretch strains the attached motor domain, and we propose that combined steric and mechanical coupling between the two domains promotes attachment of the second motor domain. This mechanism allows skeletal muscle to resist external stretch without increasing the force per motor and provides an answer to the longstanding question of the functional role of the dimeric structure of muscle myosin.
Brunello
Elisabetta
E
Laboratorio di Fisiologia, Dipartimento di Biologia Animale e Genetica, Università degli Studi di Firenze, Via G. Sansone 1, 50019 Sesto Fiorentino, Italy.
Reconditi
Massimo
M
Elangovan
Ravikrishnan
R
Linari
Marco
M
Sun
Yin-Biao
YB
Narayanan
Theyencheri
T
Panine
Pierre
P
Piazzesi
Gabriella
G
Irving
Malcolm
M
Lombardi
Vincenzo
V
D000199:Actins / Q000378:metabolism*; D000818:Animals; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D052580:Muscle Stretching Exercises; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D011896:Rana temporaria
D000199:Actins; D009218:Myosins