Actin is one of the most abundant proteins found within virtually all eukaryotic cells. As a highly conserved protein, actin plays a role in processes ranging from maintaining a cell’s internal structure to generating the forces required for muscle contraction. Actin filaments, also known as microfilaments, are part of the cell’s internal scaffolding, the cytoskeleton. The cytoskeleton provides mechanical support and enables movement within the cell and of the cell itself.
The Molecular Architecture of Actin
Actin exists in two primary forms that interconvert dynamically. The globular, monomeric form is known as G-actin, which is the basic building block of the filament. G-actin monomers contain a binding site for adenosine triphosphate (ATP), which powers the assembly process.
The second form, filamentous actin or F-actin, is a long, helical polymer formed when G-actin monomers join together. F-actin resembles a double-stranded helix, creating a flexible, strong fiber. The polymerization process creates a filament with a distinct structural polarity. This polarity features a “plus” (barbed) end where growth occurs rapidly and a “minus” (pointed) end where monomers tend to dissociate. This polarity dictates the directionality of movement and growth, which is necessary for force generation and remodeling the cytoskeleton.
The Sliding Filament Mechanism
In muscle tissue, actin is the primary component of the thin filament, which interacts with the thick filament (myosin) to generate force and contraction. Muscle contraction is explained by the sliding filament theory, where the actin and myosin filaments slide past one another. The mechanical movement is driven by the cyclical interaction between the globular heads of the myosin protein and the actin filament, forming temporary connections known as cross-bridges.
The cross-bridge cycle is a four-step process fueled by ATP hydrolysis. The cycle begins when the myosin head, bound to ADP and inorganic phosphate, attaches to a binding site on the actin filament. The release of the inorganic phosphate initiates the power stroke, pulling the attached actin filament toward the center of the muscle unit.
Following the power stroke, the myosin head releases the ADP, remaining tightly bound to the actin (rigor state). A fresh molecule of ATP then binds to the myosin head, causing the cross-bridge to detach from the actin filament. The ATP is subsequently hydrolyzed, “re-cocking” the myosin head to its high-energy position, ready to continue the cycle as long as calcium and ATP are present.
Actin’s Role in Maintaining Cell Shape and Motility
Outside of muscle cells, actin is a major component of the cytoskeleton, providing structure and enabling movement. Actin filaments form a dense network just beneath the cell membrane, called the cortex, which helps maintain the cell’s shape and provides mechanical strength. This network is highly dynamic, constantly assembling and disassembling to allow the cell to change shape rapidly in response to signals.
Actin also drives cellular movement, or motility, which is essential for processes like wound healing and immune response. For a cell to “crawl,” actin filaments polymerize at the leading edge to push the membrane forward, forming protrusions called lamellipodia (sheet-like) or filopodia (spike-like). Furthermore, actin plays a direct role in cell division, forming a contractile ring that pinches the parent cell into two daughter cells during cytokinesis.
How Actin Function is Controlled
In muscle cells, regulatory proteins, primarily troponin and tropomyosin, control the interaction between actin and myosin. Tropomyosin is a long protein that wraps around the actin filament, physically blocking the myosin-binding sites when the muscle is at rest.
Contraction is triggered by an influx of calcium ions, which bind to the troponin complex. This binding causes a change in the troponin-tropomyosin complex that moves the tropomyosin away from the myosin-binding sites, allowing the cross-bridge cycle to begin. In non-muscle cells, actin’s dynamics are controlled by accessory proteins that promote or inhibit its assembly and disassembly.
These accessory proteins include nucleating factors, like the Arp2/3 complex, which initiate the formation of new filaments. Capping proteins control filament length, ensuring the actin network is constantly remodeled for specific cellular tasks.