An introduction to the mechanism of muscle contraction
Muscle is an organ specializing in the transformation of chemical energy into movement. Movement is essential to life, and takes many forms, from cytoplasmic streaming and the growth of neurones at the cellular level, to the long distance flight of the albatross or the explosive performance of a sprinter. Although only a few families of proteins are responsible for movement in the biological world, muscle has developed to optimize this function, and is packed with movement-related proteins. There are many types of muscles, but they fall into three categories: skeletal muscle (or striated muscle), responsible for locomotion, flight etc; cardiac muscle, which has a vital role and is able to function for a century or more, without ever taking a break, and smooth muscle (or involuntary muscle) which lines the walls of the arteries to control blood pressure, or controls the digestion of food by causing movement of the intestine.
Skeletal muscle as seen under the light microscope has a striated appearance, as seen in the picture of a myofibril:
This micrograph was taken by Ronnie Burns in March 1997 with a 100x objective in brightfield/phase.
The myofibrils are about 1 micrometer thick, and are the result of dissection of single muscle cells. The striated appearance is due to the arrangement of two sets of interdigitating arrays of filaments.
The thick filaments (orange below) consist of myosin, and the thin filaments (green below) consist predominantly of actin.
The striations result from the fact that the thick and thin filaments have different refractive indices in the light microscope. The myofibrils are also birefringent.
The dark bands in the micrograph represent regions of overlap between the thin and thick filaments. The Z-line which ties the thin filaments together can also be seen. Stretching to scale two of the sarcomeres above shows the relationship between the bands and the filament arrays:
Click on the above sarcomeres to see a more detailed picture. The birefringent properties of muscle has led to the names I- and A-bands, where the I-band is isotropic and the A-band is anisotropic.
A sarcomere from a mammalian muscle is about 2.4 micrometer long at rest. It can be extended reversibly to more than 3 micrometer (as in the micrograph above), and it can shorten to less than 2 micrometer. The appearance of the striations change during shortening. The filaments do not change length during shortening (recent experiments have shown that the filaments are slightly elastic, but most of the shortening is caused by sliding). The sliding movement of the sarcomere is shown below:
The sliding of the filaments is the result of interactions between the myosin cross-bridges and the thin (actin) filaments. The cross-bridges reversibly bind to actin and produce a mechanical impulse which results in force transmission along the filaments, which either results in force production at the tendons, or results in shortening (or a combination of both).
The energy for this process comes from the hydrolysis of ATP, resulting in the release ADP and Pi. The link between movement or force and the utilization of ATP is the fundamental aspect of muscle contraction, sometimes referred to as the energy transduction process.
The areas of current research relate to understanding the link between ATP binding, hydrolysis and product release, and the production of a mechanical impulse. Little is known about these processes. The nature of crossbridge binding to the actin is crucial. Is there a single binding site, or are there several ? How does ATP binding or hydrolysis affect the nature of actin binding. Which part of the crossbridges change shape? Each myosin molecule is a double helical coil and ends in two globular heads or cross-bridge. Does each head behaves independently of the other ?
The study of muscle contraction involves the use of a large variety of biophysical techniques, in many laboratories around the world.
Such techniques range from physiological studies of muscle contraction to biochemical studies of muscle proteins and nucleotide hydrolysis and include protein crystallography, low angle x-ray diffraction, the design of mutant proteins, NMR, electron microscopy, photolysis of caged compounds, in vitro motility assays and others.
||Here is a cartoon of muscle cross-bridges
showing the relationship between the
cross-bridges and the filaments.Click on icons for a more detailed picture
|Here is a cartoon of a thick filament
showing the regular arrangement of myosin
protruding from the backbone every 14.5 nm.
There are 294 myosin molecules per thick
filament (588 ATPase sites).
With due acknowledgements to, inter alia,
G. Offer (1987)Fibrous Protein Structure
Click on icon for a more detailed picture
Click here to go back to
Daresbury or to Mike Ferenczi's laboratory home page
||X-ray diffraction of a crystal of chicken muscle myosin
has revealed the molecular structure of the crossbridges.
The fulcrum in the animation
is nothing but pure imagination. It is likely that movement is much more
distributed than that shown. There is also likely to be considerable movement
at the actin-myosin interface.
Each myosin molecule contains two peptide heavy chains
which are cleaved enzymatically to produce a myosin tail
and two globular heads or crossbridges.
The crossbridge heavy chain has a tail region (shown in blue)
around which two smaller peptides wrap.
These peptides are the light chains (yellow and red)
which stabilize, and in some cases, regulate the myosin.
With due acknowledgements to Rayment et al. (1993) Science 261: 50-58
March 1997, revised October 2001