Microfilament Structure and Composition
Microfilaments are the thinnest elements of the cytoskeleton, with a diameter of about 7 nm. They provide mechanical support, maintain cell shape, drive cell motility, and play a central role in cytokinesis. Because they're constantly assembling and disassembling, microfilaments allow cells to rapidly reshape themselves in response to signals.
Structure and polarity
Each microfilament is built from globular actin (G-actin) monomers (~42 kDa each) that polymerize into a double-helical strand called filamentous actin (F-actin).
Microfilaments are polarized, meaning the two ends are structurally and functionally different:
- The barbed (+) end is where polymerization (monomer addition) predominantly occurs.
- The pointed (−) end is where depolymerization (monomer loss) predominantly occurs.
This polarity matters because it determines the direction of filament growth, the direction myosin motors travel, and how regulatory proteins recognize each end.
Actin Dynamics and Regulation
Actin polymerization and the ATP cycle
Actin polymerization is coupled to ATP hydrolysis, and understanding that link is essential for understanding filament turnover.
- Free G-actin monomers in the cytoplasm bind ATP.
- ATP-bound G-actin has a high affinity for the barbed (+) end, so it adds there preferentially.
- Shortly after incorporation into the filament, the bound ATP is hydrolyzed to ADP + Pi, and Pi is slowly released.
- ADP-bound actin subunits accumulate toward the pointed (−) end, where they dissociate more readily.
- Released ADP-G-actin monomers exchange ADP for ATP (aided by profilin) and re-enter the pool of polymerization-competent monomers.
This continuous addition at the (+) end and loss at the (−) end is called treadmilling. It allows a filament to maintain a roughly constant length while its subunits cycle through.
Actin-binding proteins that regulate dynamics
Cells don't leave actin dynamics to chance. A set of actin-binding proteins tightly controls where, when, and how fast filaments grow or shrink.
- Profilin binds G-actin and catalyzes the exchange of ADP for ATP, recharging monomers so they're ready to add to the barbed end. It effectively accelerates polymerization.
- Cofilin (also called ADF/cofilin) binds preferentially to ADP-actin subunits within F-actin. It severs filaments and promotes disassembly, increasing the supply of free G-actin for new polymerization elsewhere.
- Arp2/3 complex nucleates new filaments by mimicking a barbed-end template. It binds to the side of an existing filament and generates a branch at a ~70° angle, creating the dense, branched actin networks found in lamellipodia.
- Capping proteins (e.g., CapZ) bind the barbed end and block further monomer addition, effectively stopping filament growth. This lets the cell control which filaments keep elongating and which don't.
- Tropomyosin stabilizes F-actin by binding along the filament groove, and it regulates myosin's access to actin.
- Gelsolin severs actin filaments and caps the newly exposed barbed ends in a calcium-dependent manner, linking actin remodeling to calcium signaling pathways.
The interplay between these proteins gives cells precise spatial and temporal control over their actin networks.
Functions of microfilaments in cells
Cell shape and mechanical support. A dense meshwork of actin filaments called the cortical actin network lies just beneath the plasma membrane. Actin-myosin interactions within this cortex generate contractile forces that maintain cell shape. Stress fibers, which are bundles of actin and myosin II, anchor to focal adhesions and allow cells to exert tension on their substrate.
Cell motility. During migration, actin polymerization at the leading edge pushes the membrane forward, forming two types of protrusive structures:
- Lamellipodia are broad, sheet-like extensions driven by branched actin networks (Arp2/3-dependent).
- Filopodia are thin, finger-like projections containing parallel actin bundles that sense the environment.
At the rear of the cell, actin-myosin contraction pulls the trailing edge forward, completing the migration cycle.
Intracellular transport. Microfilaments serve as tracks for myosin motor proteins that carry cargo through the cytoplasm. Myosin V moves toward the barbed (+) end and transports vesicles and organelles, while myosin VI is unusual in that it moves toward the pointed (−) end. This transport system is especially important in regions where microtubules don't reach, such as the cell cortex.
Cytokinesis. During cell division, a contractile ring of actin and myosin II assembles at the cell equator. Progressive contraction of this ring pinches the cell in two, completing cytokinesis.