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ActomyosinEdit

Actomyosin refers to the functional complex formed when actin filaments interact with myosin motor proteins to convert chemical energy from ATP into mechanical work. This system is central to a wide range of cellular processes, most famously muscle contraction, but also crucial for shaping cells, driving migration, and completing cell division. The actomyosin machinery is evolutionarily conserved across eukaryotes, underscoring its fundamental role in physiology and development. In muscle tissue, actomyosin activity is organized into highly ordered units called sarcomeres, enabling rapid, repetitive contractions. In non-muscle cells, actomyosin networks generate cortical tension and power dynamic rearrangements that allow cells to move, divide, and respond to their environment. actin myosin sarcomere contractile ring cell migration cytokinesis

The system relies on a division of labor between filamentous actin and various families of myosin motors. In skeletal, cardiac, and smooth muscle, a specialized form known as myosin II forms thick filaments that interact with the actin-containing thin filaments of the sarcomere. In non-muscle cells, other myosins (for example, myosin I and myosin V) participate in cargo transport and cortical remodeling while still contributing to contractile forces when paired with actin networks. The activity of myosin motors is governed by ATP binding and hydrolysis, which drives the conformational changes that produce a power stroke along actin filaments. Regulatory proteins modulate access to actin’s binding sites and tune the force and speed of contraction. ATP MLCK ROCK troponin tropomyosin actin-binding proteins

Structure and function

Core components

Actin filaments are polar polymers formed from actin monomers (G-actin) that assemble into filamentous actin (F-actin). Each filament has a fast-growing “barbed” end and a slower “pointed” end, enabling dynamic remodeling of the cytoskeleton. Myosin motors convert nucleotide energy into mechanical work as they cycle through weak and strong bindings to actin. In muscle, the interplay between actin and myosin is organized within repeating units called sarcomeres, which contain thick (myosin) and thin (actin) filaments arranged in a precise lattice. In non-muscle contexts, actin–myosin networks can organize into contractile bundles and rings that drive shape changes and division. actin F-actin G-actin sarcomere myosin II Z-disc

The cross-bridge cycle

The canonical model for actomyosin contraction is the cross-bridge cycle, a sequence of steps regulated by ATP binding, hydrolysis, and product release: - In the absence of nucleotide, myosin heads strongly bind to actin (rigor-like state). - ATP binds to the myosin head, causing detachment from actin. - ATP hydrolysis converts to ADP and inorganic phosphate (Pi), "cocking" the head into a high-energy state. - Release of Pi enables the myosin head to bind actin more tightly and execute a power stroke that moves the actin filament relative to the myosin filament. - ADP release completes the cycle, allowing another ATP to bind and start a new round. The timing of these steps determines force, velocity, and efficiency of contraction. ATP ADP cross-bridge power stroke

In muscle cells, these cycles occur in a highly cooperative, organized fashion within sarcomeres, producing rapid, synchronized shortening. In non-muscle cells, individual motors and networks generate more diverse patterns of force and movement, but rely on the same basic chemical mechanism. sarcomere contractile ring

Regulation of actomyosin activity

In muscle fibers, Ca2+ ions regulate contraction by controlling the position of the thin-filament regulatory proteins. When Ca2+ binds to the troponin TnC, tropomyosin shifts to expose myosin-binding sites on actin, permitting cross-bridge cycling. This calcium-dependent mechanism is central to the precise control of twitch and sustained contractions. In non-muscle cells, regulation often centers on phosphorylation of the myosin light chains by enzymes such as MLCK (myosin light-chain kinase) and by signaling kinases like ROCK (Rho-associated kinase), which respond to mechanical cues and biochemical signals to tune contractility and network organization. troponin tropomyosin MLCK ROCK calcium

Cellular roles

  • Muscle contraction: In skeletal and cardiac muscle, actomyosin drives shortening of sarcomeres, generating force for movements and pumping of blood. skeletal muscle cardiac muscle muscle contraction
  • Cell migration and shape changes: Actomyosin networks generate cortical tension at the cell cortex, enabling edge protrusion, retraction, and adhesion dynamics during migration. cell migration cortex
  • Cytokinesis: The contractile ring of actomyosin forms at the cell’s equator during division, constricting the membrane to separate daughter cells. cytokinesis contractile ring
  • Tissue morphogenesis and wound healing: Actomyosin-generated forces shape tissues and promote epithelial remodeling and repair. tissue morphogenesis wound healing

In disease and research

Mutations and dysregulation of actin or myosin can lead to muscle and heart disease, such as cardiomyopathies and certain myopathies. For example, changes in myosin heavy-chain genes or associated regulatory proteins can alter contractile function and resilience under stress. Research into actomyosin is also a platform for understanding fundamental motor mechanics and for developing targeted therapies that modulate contractility in disease states. cardiomyopathy hypertrophic cardiomyopathy nemaline myopathy

Experimental study and models

Actomyosin systems have been studied through a variety of approaches, including: - Reconstituted in vitro assays that isolate actin–myosin interactions and measure properties like force generation, velocity, and duty cycle. in vitro reconstitution - High-resolution imaging techniques such as electron microscopy and cryo-electron microscopy to visualize filament arrangements and motor conformations. cryo-EM electron microscopy - Single-molecule methods and gliding assays that illuminate kinetic steps and mechanical responses under controlled loads. single-molecule gliding assay - Live-cell imaging to observe actomyosin dynamics during processes like cell migration, cytokinesis, and morphogenesis. live-cell imaging

Evolution and diversity

The actomyosin system is highly conserved in eukaryotes, with multiple myosin families tailored to diverse cellular tasks. Myosin II is a key driver of contractile force in many animal cells, while other myosins specialize in cargo transport, signaling, or membrane remodeling. The core mechanism—the coupling of ATP hydrolysis to conformational changes that move along actin—has been retained while the regulatory networks and filament architectures have diversified to meet organismal needs. myosin II motor protein actin-binding proteins

Controversies and debates

As with many mature fields, actomyosin biology includes technical and interpretive debates: - The precise molecular details of the cross-bridge cycle continue to be refined, with ongoing discussion about the timing of phosphate release and the exact lever-arm mechanics across different myosin classes. Researchers debate the degree to which observed behaviors reflect a single dominant mechanism versus context-dependent variations. cross-bridge power stroke - In non-muscle cells, the balance between contractile force generation and actin turnover remains an active area of study, with questions about how cortical tension is tuned by feedback between signaling pathways and mechanical load. cell cortex actin turnover - The organization of thick-filament regulation in skeletal muscles—such as the contributions of proteins like myosin-binding protein C to thick-filament activation—continues to be clarified, as do differences among fast and slow muscle types. myosin-binding protein C skeletal muscle fiber types - Some models emphasize a highly organized, sarcomere-like arrangement even in non-muscle tissues, while others highlight more fluid, viscoelastic networks; debates center on how universal the sarcomeric view is outside classic muscle. sarcomere actomyosin network - Technological advances, including improved imaging and computational modeling, occasionally shift interpretations about force distribution, motor cooperativity, and the relative contributions of myosin isoforms to specific cellular processes. imaging computational modeling

See also