A glimpse into the story of muscle

Every time we see a phenomena/object we are not conversant with, we begin by giving it a name to start conversing about it. This rule applies across the board with a very strong emphasis in sciences. Each time there is a potentially new specimen still unrecognized, a scientific name is quickly alloted to it.

Folklore has it that long time ago, in Greece, a similar story began when the budding scientists of that era noticed a mouse moving up and down the upper arm of a disc thrower every time he exhibited his skills at the sport. To begin a simple conversation they named it - muscle, a simple diminutive version of musculus meaning mouse in Latin. Thus, was launched a whole new world of muscle studies.

Thereafter, it was recognized that the organ of motion is muscle. The understanding of muscle we have now, required long nights spent in graveyards digging bodies and studying science against the beliefs of the society then. Studying the anatomy of the human body and laying the foundations of this science of contraction has traversed from graveyards to the modern day science lab with the pipette tips and the microscope. It was in 1700s that Galvani and Volta recognized that movement of charges aka biological electric currents underlie contraction and cause movement of limbs.

It was only in 1864 that Kuhne isolated a viscous protein and named it mysoin. Amidst war years and complete scientific isolation, Albert Szent Gyorgyi and his colleagues established that "myosin" consisted of two molecules of varying viscosity. In parallel, Needham et al. discovered the effect of ATP on Kuhne's myosin independently. The two groups were never able to communicate. But a molecular motor driving movement had been discovered. A century later Actin molecules were discovered by Straub in 1942. The molecular foundation of the muscle had now been laid.

In 1953, the milestone of muscle research was established by Huxley and Huxley when they proposed the Sliding Filament Theory of muscle. It was based on the observation of constancy of the length of the A-band and the shortening of the I-band during contraction. Using interference microscopy and phase contrast miscroscopy it was shown that molecular motors do not change in length while contracting but thin and thick filaments slide over one another causing the change in muscle length thereby resulting in contraction. Thus heralded a new era in muscle science.

The race to discover the regulators of contraction, the structure of these threads, the ATP utilization of this phenomena had just begun. Lymn and Taylor proposed the cross-bridge cycle in 1971, breaking down contraction in steps of ATP utilization. Tropomyosin was discovered by Bailey in 1946. That calcium removal induced relaxation was discovered by Marsh and Bendell. And to complete the jigsaw Ebashi et al. unraveled Troponins.

I embarked on this journey when I did my rotation in Dr. De Tombes lab and saw a string of sarcomeres beautifully suspended between two 7-10 micron thin glass needles. The string is called a myofibril.  The shadow of a darkly coated glass needle fell exactly in between a pair of identical photodiodes when this string did not contract. As soon as calcium hit this string, it contracted, pulled the dark glass needle and its shadow biased towards one photodiode, thereby enabling us to record the force! It exerts a force of about 50nN/mm2. To understand this beautiful wonder, I delved deep into the past origins of this story.

Justice cannot be done to this discovery of the muscle and its molecules in a short one page entry. However, one can fathom the process of scientific discovery and the eons it entails as each piece of the big puzzle falls in place. What I have written here is just a peek into this wonderful world. The work on understanding muscle is still far from complete. A new brick has to be baked everyday and molded to perfection to be laid into the wall.

Follow up Reads:

1. Prime mover by Steven Vogel

2. The Early History of the Biochemistry of Muscle Contraction - Andrew G. Szent-Gyorgyi, J. Gen Physiol. Vol 123 (2004) 631-641.