The Exquisite Machines in Muscle Contraction: A Hierarchical and Geometric Symphony
It is not by chance that Neil Gershenfeld described molecular biology as being dominated by geometry. This point is strongly reinforced when we explore the world of muscle contraction, which exemplifies the hierarchical construction of systems and the importance of geometry in molecular interactions.
So molecular biology is dominated by geometry. That’s why the protein folding is so important, that the geometry gives the function.
And there’s this hierarchical construction of as you go through primary, second, tertiary, quaternary, the shapes of the molecules make the shape of the molecular machines. And they really are exquisite machines. If you look at how your muscles move, if you were to see a simulation of it, it would look like a improbable science fiction cyborg world of these little walking robots that walk on a discreet lattice.
They’re really exquisite machines. And then from there, there’s this whole hierarchical stack of once you get to the top of that, you then start making organelles that make cells that make organs through the stack of that hierarchy.
Disclaimer: This post was written with ChatGPT.
Source: The Mechanism of Muscle Contraction: Sarcomeres, Action Potential, and the Neuromuscular Junction.
The organization of muscle begins with skeletal muscles, comprised of fascicles. Each fascicle contains muscle fibers, the individual muscle cells. These fibers, when looked at more closely, contain myofibrils, which further break down into myofilaments arranged into sarcomeres. The sarcomere is the fundamental contractile unit of muscle and demonstrates a complexity arising from its molecular geometry.
The sarcomere is split into several regions, each with its distinct composition and function. Thick filaments containing the protein myosin stretch across a region known as the A-band. Thin filaments, predominantly made of actin, stretch across the I-band and into the A-band. Elastic filaments, made of the protein titin, extend from the Z discs to the thick filament and beyond, acting as the core of the thick filament. The assembly of these components creates the distinct striated appearance of skeletal muscle.
The myosin and actin are the key players in muscle contraction. Myosin features two globular heads pointing outwards with ATP and actin binding sites, enabling them to form cross-bridges with the actin filament. Actin filaments, in their relaxed state, have their myosin binding sites blocked by tropomyosin, with the protein complex troponin attached.
The contraction process starts with a signal from the nervous system, leading to a cascade of chemical reactions at the neuromuscular junction, where the nerve meets the muscle. This junction contains axon terminals, which release the neurotransmitter acetylcholine into the synaptic cleft, initiating an influx of sodium ions and an efflux of potassium ions, ultimately leading to a change in the membrane potential.
This change in electrical potential, or depolarization, causes the propagation of an action potential across the muscle cell membrane (sarcolemma) and down into T-tubules, initiating a rise in cytosolic calcium ion levels. These calcium ions bind to troponin, causing a conformational change that unblocks the myosin binding sites on actin. This allows for cross-bridge cycling — the pivotal process where myosin heads pull the actin filament towards the center of the sarcomere, shortening the muscle cell and resulting in contraction.
This exquisite machinery perfectly exemplifies Gershenfeld’s idea of hierarchical construction, from the molecular arrangement of proteins to the formation of muscle fibers, and finally to the large-scale movement of our bodies. It also encapsulates the fundamental role of geometry in determining molecular function — the conformational changes and spatial organization of myosin and actin filaments, and their interactions, govern the mechanics of muscle contraction. This system can indeed be visualized as an “improbable science fiction cyborg world of these little walking robots,” demonstrating how molecular geometry constructs life’s exquisite machines.
