Actomyosin is a molecular motor complex found in nearly all living organisms, from single-celled organisms to complex animals. This protein assembly generates mechanical force and movement within cells, contributing to a wide range of biological processes. Its ability to convert chemical energy into mechanical work makes it a versatile component of cellular machinery, essential for maintaining cellular function and structure.
The Building Blocks of Actomyosin
Actomyosin is primarily composed of two proteins: actin and myosin. Actin is one of the most abundant proteins in eukaryotic cells, existing in two forms: globular (G-actin) and filamentous (F-actin). G-actin monomers can spontaneously assemble into F-actin, which are thin, flexible helical filaments approximately 7 nanometers in diameter. These filaments provide structural support and act as tracks for myosin.
Myosin proteins are a diverse family of molecular motors. A typical myosin molecule has a head domain, a neck region, and a tail domain. The head domain binds to actin and converts chemical energy from ATP into mechanical movement. The tail domain interacts with other molecules or cellular structures, enabling the transport of cellular components. Myosin II is a dimer with two heavy chains and two pairs of light chains, forming a structure with two globular heads and a coiled-coil tail.
How Actomyosin Powers Muscle Contraction
Muscle contraction is driven by the sliding filament theory, where actin and myosin filaments slide past each other. Within muscle cells, these proteins are arranged into repeating units called sarcomeres, the smallest contractile units. Actin forms thin filaments, while myosin forms thick filaments, and these interdigitate within the sarcomere.
The contraction cycle begins with myosin heads binding to actin, forming cross-bridges. This binding is regulated by calcium ions. When a muscle receives a signal to contract, calcium ions are released into the muscle cell cytoplasm. These calcium ions bind to troponin, a protein associated with actin, causing a shift in tropomyosin that exposes the myosin-binding sites on the actin filaments.
Once the binding sites are exposed, myosin heads, having hydrolyzed ATP, attach to actin. The release of ADP and phosphate triggers a conformational change in the myosin head, known as the power stroke, which pulls the actin filament towards the center of the sarcomere. A new ATP molecule then binds to the myosin head, causing it to detach from actin, allowing the cycle to repeat. This continuous binding, pulling, and detaching action shortens the sarcomere and, consequently, the entire muscle fiber.
Actomyosin’s Diverse Roles Beyond Muscle
Beyond its role in muscle contraction, actomyosin plays diverse roles in non-muscle cells, contributing to various cellular activities. The same fundamental contractile mechanism observed in muscle cells adapts for these different functions. This adaptability highlights the versatility of the actin-myosin interaction.
One significant role is in cell division, specifically during a process called cytokinesis. At the end of mitosis, a contractile ring composed of actin filaments and myosin II forms around the middle of the dividing cell. The contraction of this actomyosin ring creates a cleavage furrow, which gradually pinches the cell in two, ensuring that each daughter cell receives a complete set of genetic material.
Actomyosin also drives cell migration, a process fundamental to wound healing, immune responses, and embryonic development. Non-muscle myosin II generates the contractile forces that enable cells to change shape and move across surfaces. This involves the coordinated assembly and disassembly of actin networks and the pulling action of myosin, allowing cells to extend protrusions, adhere to surfaces, and retract their rear, resulting in directed movement.
Actomyosin is also involved in intracellular transport, facilitating the movement of various cargoes, such as vesicles and organelles, within the cell. Myosin motors “walk” along actin filaments, carrying their attached cargo to specific destinations within the cellular environment. This transport system is important for maintaining cellular organization and delivering molecules where they are needed for cellular processes.
Implications for Health and Medicine
Disruptions in actomyosin function can have serious consequences for human health, leading to a range of diseases. Since actomyosin is essential to muscle contraction, abnormalities in its components can cause muscle disorders. For example, mutations in the ACTA1 gene, which codes for skeletal alpha-actin, are linked to actin-accumulation myopathy, a condition characterized by severe muscle weakness and poor muscle tone. Such mutations can impair muscle contraction by affecting how actin binds to ATP or by leading to abnormal thin filament formation.
Myosinopathies, which involve the accumulation of myosin or mutations in myosin genes like MYH7, can also result in congenital muscle weakness. Beyond muscle-specific conditions, the involvement of actomyosin in cell motility makes it relevant to diseases like cancer. The ability of cancer cells to spread, known as metastasis, often relies on their capacity to change shape and move through tissues. Actomyosin contractility plays a role in these invasive processes, including cancer cell migration, invasion into surrounding tissues, and colonization of new organs. Modulating actomyosin activity is thus being explored as a potential therapeutic strategy to combat metastatic disease.