Actomyosin: How It Shapes Cells and Powers Movement

Cells constantly change shape and move, essential processes for development, wound healing, and immune responses. A key driver of these dynamic behaviors is actomyosin, a complex of actin filaments and myosin motor proteins that generates contractile forces within cells. Understanding how actomyosin functions provides insight into fundamental biological processes and diseases where cell movement goes awry, such as cancer metastasis.

Structural Organization Of Actomyosin

The actomyosin network is a dynamic system that underpins cellular contractility. It consists of actin filaments, which provide a scaffold, and myosin motor proteins, which generate force by interacting with actin. Actin filaments are composed of polymerized globular actin (G-actin) subunits, forming helical filaments (F-actin) that serve as tracks for myosin movement. These filaments adopt different architectures depending on cellular needs, including linear bundles, branched networks, and contractile rings. Their organization is regulated by actin-binding proteins such as formins, which promote filament elongation, and the Arp2/3 complex, which facilitates branching.

Myosin II, the primary motor protein in actomyosin contractility, operates as a hexameric complex with two heavy chains, two essential light chains, and two regulatory light chains. The heavy chains contain motor domains that hydrolyze ATP to generate movement along actin filaments, while the tail domains mediate filament assembly. Myosin II molecules self-associate into bipolar filaments, allowing them to pull on actin filaments in an antiparallel fashion, leading to contraction. The assembly of myosin filaments is modulated by phosphorylation of regulatory light chains, which influences filament stability and motor activity. This phosphorylation is controlled by kinases such as myosin light chain kinase (MLCK) and Rho-associated protein kinase (ROCK), ensuring contractile forces respond to cellular signals.

The spatial organization of actomyosin varies across cellular structures. In stress fibers, actin and myosin filaments are arranged in a periodic pattern, with myosin filaments interspersed between actin filaments to facilitate contraction. In the cortex, a thin layer beneath the plasma membrane, actomyosin forms a meshwork that regulates cell shape and mechanical properties. During cytokinesis, actomyosin assembles into a contractile ring that drives the physical separation of daughter cells. Its ability to reorganize in response to mechanical and biochemical cues allows cells to adapt to their environment.

Mechanisms Of Force Generation

Actomyosin-driven force production relies on molecular interactions between actin filaments and myosin motor proteins, which convert chemical energy from ATP hydrolysis into mechanical work. Myosin II binds to actin in a weakly attached state with ATP occupying the active site. Upon ATP hydrolysis, the myosin head undergoes a conformational change, positioning it further along the actin filament. The release of inorganic phosphate strengthens the actin-myosin interaction, triggering the power stroke—a structural shift in the myosin head that propels the filament. ADP dissociation allows ATP to rebind, causing myosin to detach and reset for the next cycle. This cyclical activity generates contractile forces that drive cellular movement and shape changes.

The magnitude and spatial distribution of force generation are tightly regulated by myosin filament assembly and actin network organization. Myosin II molecules self-assemble into bipolar filaments, where motor heads on opposite ends pull actin filaments toward each other, creating contractile tension. The density and length of these filaments influence overall force output, with larger assemblies producing stronger contractions. Actin filament architecture also plays a role, as linear bundles promote efficient force transmission, while branched networks provide structural support. Crosslinking proteins such as filamin further modulate actin network stiffness, ensuring generated forces are appropriately transmitted across the cytoskeleton.

Cellular contractility is also influenced by the mechanical properties of the environment. Substrate stiffness affects actomyosin activity through mechanosensitive pathways that adjust myosin filament assembly and actin organization. Cells on rigid surfaces exhibit higher myosin recruitment and contractile force compared to those on softer substrates. External forces acting on cells can reinforce actomyosin contractility through mechanotransduction mechanisms, where tension-dependent signaling cascades enhance myosin motor activity and filament stability.

Regulation By Signaling Pathways

Actomyosin contractility is finely tuned by signaling pathways that modulate myosin motor function and actin filament organization. The Rho family of small GTPases, particularly RhoA, is a key regulator of actomyosin contractility. RhoA signaling enhances myosin activity through ROCK, which phosphorylates the myosin regulatory light chain (MLC) to increase motor function while inhibiting myosin phosphatase, prolonging contractile force generation.

Calcium signaling also plays a significant role in actomyosin regulation through calcium/calmodulin-dependent MLCK. Elevated intracellular calcium levels activate MLCK, leading to MLC phosphorylation and enhanced myosin-driven contraction. This pathway allows actomyosin dynamics to rapidly adjust to changing conditions. While MLCK primarily governs localized contractile responses, it operates in concert with RhoA-ROCK signaling to fine-tune force production.

Growth factors and extracellular signals influence actomyosin function by engaging signaling cascades such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways. These pathways regulate actin polymerization and myosin filament assembly by modulating actin-binding proteins and myosin motor activity. PI3K signaling promotes the recruitment of actin nucleators like formins, shaping the actin network to support contractile forces. Meanwhile, MAPK signaling alters myosin phosphorylation status, affecting filament stability and motor efficiency. The integration of these pathways allows cells to coordinate actomyosin activity in response to external cues.

Role In Cell And Tissue Morphogenesis

Actomyosin-driven contractility plays a fundamental role in shaping cells and orchestrating tissue development. During embryogenesis, coordinated actomyosin activity generates mechanical forces that drive epithelial folding, a crucial step in forming structures such as the neural tube and optic cup. Myosin II accumulates at specific regions of the epithelial sheet, creating localized contractions that induce bending and invagination. These forces are balanced with adhesion molecules like cadherins, ensuring tissue integrity while allowing dynamic remodeling. Disruptions in actomyosin function during these processes have been linked to congenital defects.

As tissues mature, actomyosin-mediated tension regulates cell intercalation, a mechanism that elongates and refines tissue architecture. This process is particularly evident in convergent extension, where cells rearrange by exerting directional forces on their neighbors, driving tissue elongation without increasing cell proliferation. Studies in model organisms such as Drosophila and Xenopus have shown that actomyosin contractility is periodically pulsed, allowing cells to progressively reposition while maintaining structural coherence. The dynamic assembly and disassembly of actomyosin networks enable tissues to achieve precise morphological outcomes.

Actomyosin In Non-Muscle Functions

Beyond muscle contraction, actomyosin drives mechanical forces in non-muscle cells, enabling diverse cellular behaviors. In migrating cells, actomyosin contractility regulates protrusion-retraction cycles at the leading edge, coordinating movement through adhesion and cytoskeletal remodeling. The actomyosin cortex, a contractile layer beneath the plasma membrane, generates tension that influences cell polarity and directional movement. This is particularly evident in mesenchymal migration, where actomyosin-mediated stress fibers provide traction forces against the extracellular matrix, and in amoeboid migration, where actomyosin contractility propels cells through confined spaces by generating cortical tension. These mechanisms are essential in processes such as embryonic development, wound healing, and pathological cell invasion.

Actomyosin also plays a role in intracellular transport and organelle positioning. Cytoplasmic streaming in plant cells relies on myosin-driven transport of organelles along actin filaments, optimizing nutrient distribution. In animal cells, actomyosin dynamics contribute to endocytosis by generating contractile forces that facilitate vesicle scission and trafficking. During mitosis, actomyosin-driven cortical tension helps position the mitotic spindle, ensuring accurate chromosome segregation. These functions illustrate the versatility of actomyosin, demonstrating its involvement in shaping cellular architecture and intracellular organization.