For Biophysics Week, members of the Early Careers Committee have written short summaries of classical biophysics studies, accessible to scientists and non-scientists alike.

This lay summary about muscle contraction and sliding filaments was written by Early Careers Committee Member Anthony Cammarato, Johns Hopkins University.

Muscle contraction and sliding filaments

Our heart and skeletal muscles contain intricately organized cells that generate the forces required to move blood and bones. Myofibrils are elongated substructures of muscle cells that are comprised of a repeating array of individual contractile units known as sarcomeres. Within each sarcomere, the highly-ordered arrangement of myosin- and actin-containing filaments are responsible for the striated “banding” appearance of the cells when viewed under a microscope. Before the 1950s, it was widely accepted that force production and muscle contraction resulted from a shortening of myosin filaments. However, on May 22, 1954 two classic papers by Andrew Huxley and Rolf Niedergerke and Hugh Huxley (no relation to Andrew) and Jean Hanson were published in the journal Nature that described the molecular basis of muscle contraction. Huxley and Niedergerke studied intact frog muscle cells, which unfortunately are too thick to reliably measure specific features by conventional light or phase contrast microscopy. Therefore, they used a novel interference microscope and demonstrated that the width of the myosin filament-containing “A-bands” stayed constant following passive cell stretches and during contraction. Huxley and Hanson obtained their results using light-microscopy and isolated myofibrils, which are extremely thin relative to whole muscle cells and, thus, are better suited for conventional imaging. They also, independently, established the constancy of the A-band width by showing that contracting sarcomeres along a myofibril shortened roughly 50% yet the A-bands’ lengths were unchanged. Huxley and Hanson additionally extracted myosin from the A-bands, leaving arrays of actin filaments, and demonstrated the role of adenosine triphosphate (ATP) hydrolysis, which provides energy to drive biological processes, in powering contraction. To account for their observations, both groups surmised that muscle contraction was not caused by A-band (i.e. myosin filament) shortening, but rather by the sliding of actin relative to myosin filaments, whose lengths remained constant. This sliding was proposed to be powered by forces generated at a series of points in the overlap region of the two filament types. Each point, or “cross-bridge”, arising from the myosin filament uses the energy liberated from splitting ATP to cyclically attach to and pull actin past myosin filaments. These two papers defined the sliding filament model of muscle contraction and were the first to demonstrate that the generation of force and cellular shortening could be explained by a fundamental interaction between two distinct proteins. Despite not gaining immediate acceptance, today the sliding filament theory is widely recognized as one of the most seminal contributions ever to the field of muscle research.

See: Huxley, A.F., and R. Niedergerke. 1954. Structural changes in muscle during contraction; interference microscopy of living muscle fibers. Nature. 173:971–973

Huxley, H., and J. Hanson. 1954. Changes in the cross-striations of muscle during contraction and stretch and their structural interpretation. Nature. 173:973–976, 247, 741.