Laboratory of Muscle Biophysics

Professor Michael Ferenczi, Head of Group

The way we move, the way the heart pumps blood around our body have always been topics of fascination. Greek records show that physicians in antiquity already pondered the topic, and misunderstandings and superstitions prevailed until the work of the early anatomists in the Renaissance and the great physiologists from the 16th century. A wonderful historical account of the development of this research area is given by Dorothy M. Needham in her book 'Machina carnis', Cambridge University Press, 1971, ISBN 0 521 07974 8.

Compound monocular microscope (late 19th century)

Nowadays, we have scientific tools that could not have been dreamed of by our forebears, and we can delve deeper into the molecular mechanisms by which energy derived from our food is transformed into the fuel that powers our movements. When we think of movement, the first that spring to mind are the movements of our limbs, hands and feet, and the movement of our chest when we breathe. All these movements are made possible by our striated muscles, so called because of the transverse striations when observed in the light microscope.

The heart too is a striated muscle with special properties. Other muscles do not have a striated appearance and are called smooth muscles. These control blood flow by changing the diameter of arteries, control the movement of our gut, the flow of urine and the tone of our bronchi. All muscles are powered by protein assemblies known as molecular motors. In skeletal muscles, these molecular motors are packed in regular, three-dimensional arrays of filaments into muscle cells. These filament arrays give the muscles their striated appearance when viewed in the light microscope. The high packing order maximises the effectiveness of the cells for power and speed. The heart too is a specialised striated muscle. In smooth muscles, the molecular packing of the motors is less regular and dense, and the contraction is slower, and often not under voluntary control, but automatic, regulated by our autonomic nervous system.

Skeletal muscle fibre observed in a confocal microscope. Actin filaments are labelled with Rhodamine-Phalloidin (red) and the myosin filaments are labelled with Alexa488 on the Essential Light Chains to highlight the A-bands. The striations repeat distance is 2.4 um. (Caorsi et al., 2010)

Besides in muscle cells which are specialised to perform large scale movement, movement is essential to all living cells, and takes many forms. The movement of chromosomes during mitosis, the formation of the cleavage furrow during cell division, the movement of vesicles to distribute components to all parts of the cells and to export products such as hormones into the blood stream, the movement of nerve cell axons to reach target organs, the flow of cytoplasm in plant cells, the movement of white blood cells in our tissues, the uncontrolled movement of cancer cells during metastasis, the gobbling-up of bacteria by cells of our immune system. All these types of movements are performed by proteins of the myosin family moving along actin filaments, or by members of a few other families such as kinesins and dyneins which move along microtubules.

In the pages that follow, I give a brief description of the molecular mechanism of muscle contraction. I highlight the important mysteries which we are trying to solve, and the methodologies we develop to address these problems.

A brief introduction to muscle
How does strain affect the contraction mechanism?
Muscle shortening, heat and stretch
Structural changes in the myosin cross-bridge
Low angle X-ray diffraction: seeing cross-bridges move in reciprocal space
Muscle fibre types
Cardiac muscle