1. Muscles Shorten Even Though the Thick Band Stays the Same Length
On May 22, 1954, two papers appeared side by side in the scientific journal Nature. One was by the group of Andrew Huxley and Niedergerke, and the other by Hugh Huxley and Hanson. They were separate groups, and the two Huxleys were not relatives [1]. In the observations by Hugh Huxley and his team, even though the segments of the myofibrils (sarcomeres) shortened, the length of the thick band containing myosin (the A-band) remained the same [2]. The shortening was thought to be caused by the thin actin threads sliding in between the thick bands [2]. Instead of the threads themselves shrinking, they slide past each other, increasing their overlap. This idea became known as the "sliding filament theory." But what are these two types of threads made of?
2. The Discovery of Actin and Muscle Threads That Contract Outside the Body
Let us go back in time. In 1942, at the Szent-Györgyi laboratory in Szeged, Hungary, a substance called "myosin B" was found to be a compound of myosin A and another substance. This other substance was named "actin," and Straub successfully purified it [3]. When an extract of muscle containing ATP was added to the purified threads, the threads contracted. It is said that when ATP was added again to the extract, the ability to contract returned [3]. Szent-Györgyi later recalled in 1963 that seeing this for the first time was one of the most thrilling moments of his life [3]. He had managed to make parts of a moving muscle contract in an experiment outside the body. So, how do the threads pull each other?
3. How the Myosin Head Repeats "Grab, Pull, Release"
The myosin threads have protruding parts called cross-bridges. It is explained that sliding occurs because these cross-bridges attach to the actin threads, pull, and then detach. The order is that when ATP attaches, the bridge detaches, and when ATP is broken down, the bridge attaches again and pulls [1]. This is similar to pulling a rope hand-over-hand: you pull with one hand, let go and switch grip, then pull again. However, myosin does not move its "hands" in large motions like a person; it is a much smaller molecular movement. Here, a question arises. Is ATP used only for "pulling"? Or does it have another role?
4. Why Muscles Stiffen After Death: ATP Runs Out and Myosin Cannot Let Go
ATP is needed not just for pulling, but also for releasing the grip. When ATP is gone, myosin and actin remain bound together. When new ATP binds to myosin, the cross-bridge detaches [4]. Rigor mortis, the stiffening of the body after death, is explained as being caused by the depletion of ATP in the muscles, leaving the threads bound together. The time when the body begins to stiffen and when it loosens varies depending on the environment and the individual [4]. Living muscles continue to "grab, pull, and release" while replenishing ATP. So, who decides when to contract and when to rest?
5. Setsuro Ebashi's Discovery That Calcium Signals Trigger Muscle Contraction
The contraction of skeletal muscle and the heart is regulated by changes in the concentration of calcium ions inside the cells. This phenomenon was discovered in the 1960s by Setsuro Ebashi and his team at the University of Tokyo Medical School [5]. Troponin was also found by Ebashi and his team at this time. Troponin, together with tropomyosin, suppresses the pulling between myosin and actin when calcium is absent. When calcium binds, this suppression is lifted, and contraction occurs [6]. The year of discovery is described differently in various sources, either as the 1960s or specifically 1965. It was a Japanese researcher who discovered the role of calcium in regulating muscle contraction. So, how large is the movement of a single pull of the threads?
6. Measuring the Movement of One Myosin Molecule with Optical Tweezers
In 1994, Finer, Simmons, Spudich, and others used optical tweezers to measure the movement of a single myosin molecule. They reported that under low load, a stepwise movement of an average of about 11 nm was observed, and under conditions measuring force, an average force of 3 to 4 pN was recorded [7]. 11 nm is about 1/90,000th of a millimeter. These figures are averages, and the movement in each instance is not always the same. The threads slide, ATP is used not only for pulling but also for releasing, and calcium sends the signal. The large flow of muscle movement connects down to the movement of invisible molecules.
7. Try "Grab, Pull, Release" Yourself by Pulling a String Hand-Over-Hand
Place a long string straight on a desk and try pulling it toward you with one hand, hand-over-hand. Slowly repeat "grab, pull, release" to bring it closer. This is a rough analogy for what the myosin heads are doing. If you want to read the original source, the announcement by the Japan Science and Technology Agency (JST) introducing the discoveries by Setsuro Ebashi and his team is available in Japanese [5].