Muscle contraction is a fundamental biological process that allows for all forms of bodily movement, from a subtle blink to powerful leaps. This intricate action relies on a precise sequence of molecular events within muscle cells, often referred to as the myosin cycle or cross-bridge cycle. This cycle represents the repeated interaction between specific proteins, leading to the shortening of muscle fibers and the generation of force.
Key Molecular Players
Muscle contraction involves several specialized proteins. Myosin is a motor protein, forming thick filaments within muscle cells and acting as the primary force generator. It possesses a globular head region capable of binding to other proteins and utilizing energy.
Actin forms thin filaments, serving as the track along which the myosin heads move. These thin filaments are helical structures that provide binding sites for myosin. Associated with actin are two regulatory proteins: tropomyosin and troponin.
Tropomyosin is a long, fibrous protein that wraps around the actin filament, covering the myosin-binding sites when the muscle is at rest.
Troponin is a complex of three subunits attached to tropomyosin. One subunit binds to tropomyosin, another to actin, and a third binds calcium ions. The energy for the myosin cycle is supplied by adenosine triphosphate (ATP), the universal energy currency of cells. Myosin heads have binding sites for both actin and ATP.
Mechanism of the Myosin Cycle
The myosin cycle, also known as the cross-bridge cycle, describes the repetitive interaction between myosin and actin that results in muscle shortening. This cycle begins with the myosin head “cocked” or energized, having hydrolyzed ATP into adenosine diphosphate (ADP) and an inorganic phosphate (Pi). In this state, the myosin head is in a high-energy configuration, ready to bind to actin.
Attachment
The first step, attachment, occurs when the energized myosin head forms a cross-bridge with an exposed binding site on the actin filament. ADP and Pi remain attached to the myosin head at this point.
Power Stroke
Following attachment, the power stroke takes place. During this phase, the inorganic phosphate (Pi) is released from the myosin head, which triggers a conformational change in the myosin. The myosin head pivots or swivels, pulling the actin filament approximately 10 nanometers (nm) toward the center of the sarcomere, the basic contractile unit of muscle. This movement generates the force for muscle contraction, and ADP is then released from the myosin head.
Detachment
A new ATP molecule binds to the myosin head, causing it to release from the actin filament. Without ATP, the myosin head would remain tightly bound to actin, a state observed in rigor mortis.
Cocking/Recovery
Finally, the cocking or recovery phase prepares the myosin head for another cycle. The newly bound ATP is hydrolyzed into ADP and Pi by an enzyme called ATPase located on the myosin head. The energy released from this hydrolysis re-cocks the myosin head, moving it back into its high-energy, ready-to-bind position. The ADP and Pi remain attached to the myosin head, allowing the cycle to repeat.
Control of Muscle Contraction
Muscle contraction is controlled primarily by the concentration of calcium ions (Ca2+). In a relaxed muscle, the myosin-binding sites on the actin filaments are blocked by the regulatory protein tropomyosin. This prevents the myosin heads from attaching to actin, thus inhibiting the myosin cycle.
When a muscle receives a signal to contract, calcium ions are released into the muscle cell’s cytoplasm from specialized storage organelles. These calcium ions then bind to troponin, one of the regulatory proteins associated with actin. The binding of calcium to troponin causes a conformational change in the troponin complex.
This change in troponin’s shape leads to a shift in tropomyosin, moving it away from the myosin-binding sites on the actin filament. With these sites now exposed, the myosin heads are free to bind to actin, initiating the cross-bridge cycle and leading to muscle contraction. When the signal to contract ceases, calcium ions are actively pumped back into storage, reducing their concentration in the cytoplasm. This removal of calcium causes troponin and tropomyosin to return to their original positions, re-covering the myosin-binding sites on actin and effectively turning off the myosin cycle, allowing the muscle to relax.