Looking at Muscle Contraction

H. Huxley and J. Hanson, 1954, Nature 173:973–976

The contraction and relaxation of skeletal muscles allow us to perform all of our daily tasks. How do these processes happen? Scientists have long looked to see how fused muscle cells, called myofibrils, differ from other cells that cannot perform powerful movements. In 1954, Jean Hanson and Hugh Huxley published their microscopy studies on muscle contraction, which demonstrated the mechanism by which it occurs.

Background

The ability of muscles to perform work has long been a fascinating process. Voluntary muscle contraction is performed by skeletal muscles, also called striated muscles because of their appearance when viewed under the microscope. By the 1950s, biologists studying myofibrils had named many of the structures they observed under the microscope. One contracting unit, called a sarcomere, is made up of two main regions, called the A band and the I band. The A band contains two darkly colored thick striations and one thin striation. The I band is made up primarily of light-colored striations, which are divided by a darkly colored line known as the Z disk. Although these structures had been characterized, their role in muscle contraction remained unclear. At the same time, biochemists tried to tackle this problem by looking for proteins that are more abundant in myofibrils than in nonmuscle cells. They found muscles to contain large amounts of the structural proteins actin and myosin in a complex with each other. Actin and myosin form polymers that can shorten when treated with adenosine triphosphate (ATP).

With these observations in mind, Hanson and Huxley began their study of cross striations in muscle. In a few short years, they united the biochemical data with the microscopy observations and developed a model for muscle contraction that still holds true today.

The Experiment

Hanson and Huxley primarily used phase-contrast microscopy in their studies of skeletal muscles that they isolated from rabbits. The technique allowed them to obtain clear pictures of the sarcomere and to take careful measurements of the A and the I bands. By treating the muscles with a variety of chemicals, then studying them under the phase-contrast microscope, they were able to successfully combine biochemistry with microscopy to describe muscle structure as well as the mechanism of contraction.

In their first set of studies, Hanson and Huxley employed chemicals that are known to specifically extract either myosin or actin from myofibrils. They first treated myofibrils with a chemical that specifically removes myosin from muscle and then used phase-contrast microscopy to compare these myofibrils with untreated myofibrils. In the untreated muscle, they observed the previously identified sarcomeric structure, including the darkly colored A band. When they looked at the myosin-extracted cells, however, the darkly colored A band was not observed. Next they extracted actin from the myosin-extracted muscle cells. When they extracted both myosin and actin from the myofibril, they could see no identifiable structure in the cell under phase-contrast microscopy. From these experiments, they concluded that myosin is located primarily in the A band, whereas actin is found throughout the myofibril.

With a better understanding of the biochemical nature of muscle structures, Huxley and Hanson went on to study the mechanism of muscle contraction. They isolated individual myofibrils from muscle tissue and treated them with ATP, which caused the myofibrils to contract at a slow rate. Using this technique, they could take pictures of various stages of muscle contraction observed using phase-contrast microscopy. They could also mechanically induce stretching by manipulating the coverslip, which allowed them to observe the relaxation process. With these techniques in hand, they examined how the structure of the myofibril changes during contraction and stretching.

Huxley and Hanson first treated myofibrils with ATP, then photographed them under phase-contrast microscopy. These pictures allowed them to measure the lengths of both the A band and the I band at various stages of contraction. When they looked at myofibrils freely contracting, they noticed a consistent shortening of the lightly colored I band, whereas the length of the A band remained constant. Within the A band, they observed the formation of an increasingly dense area throughout the contraction.

Next the two scientists examined how the myofibril structure changes during a simulated muscle stretch. They stretched isolated myofibrils mounted on glass slides by manipulating the coverslip. They again photographed the myofibrils under phase-contrast microscopy and measured the lengths of the A and the I bands. During stretching, the length of the I band increased, rather than shortened, as it had in contraction. Once again, the length of the A band remained unchanged. The dense zone that formed in the A band during contraction became less dense during stretching.

From their observations, Hanson and Huxley developed a model for muscle contraction and stretching (Figure 1). In their model, the actin filaments in the I band are drawn up into the A band during contraction, and thus the I band becomes shorter. This allows for increased interaction between the myosin located in the A band and the actin filaments. As the muscle stretches, the actin filaments withdraw from the A band. From these data, Hanson and Huxley proposed that muscle contraction is driven by actin filaments moving in and out of a mass of stationary myosin filaments.

Discussion

By combining microscopic observations with biochemical treatments of muscle fibers, Hanson and Huxley were able to describe the biochemical nature of muscle structures and outline a mechanism for muscle contraction. A large body of research continues to focus on understanding the process of muscle contraction. Scientists now know that muscles contract by ATP hydrolysis, which drives a conformational change in myosin that allows it to pull on actin. Researchers are continuing to uncover the molecular details of this process, whereas the mechanism of contraction proposed by Hanson and Huxley remains in place.