Filopodia

Filopodia are slender, actin-rich cellular protrusions that extend from the surface of many cell types. They function as sensory and exploratory structures, probing the extracellular environment to guide migration, adhesion, and cell–cell interactions.

Structure and composition: Filopodia are typically 0.1 to 0.3 micrometers in diameter and can reach several micrometers in length. Their core consists of tightly packed, parallel bundles of filamentous actin (F-actin), stabilized by actin-bundling proteins such as fascin and fimbrin. The tip contains actin filaments in a growth zone with regulatory proteins that promote elongation, while the membrane envelops the protrusion.

Biogenesis and dynamics: Filopodium formation is driven by activation of Cdc42 and downstream effectors, including formins such as mDia2 and the Ena/VASP family, which promote polymerization at the growing tip. The Arp2/3 complex, which generates branched networks in lamellipodia, is less central within the central filopodial bundle, though it may contribute at the base. Filopodia often arise from preexisting lamellipodial networks but can also form de novo, and they continually extend and retract in response to cues.

Functions: They enable environmental sensing, chemotaxis, and directional migration. In neurons, filopodia from growth cones guide axon pathfinding. In other cell types, they facilitate adhesion, ligand capture, and exploration of substrates and neighboring cells.

Regulation: Rho family GTPases, especially Cdc42 and Rac, regulate formation; actin regulators such as IRSp53, N-WASP, and VASP coordinate actin assembly. Phosphoinositides and mechanical cues also modulate filopodial dynamics.

Clinical and research relevance: Filopodia are involved in development, wound healing, and cancer cell invasion, where dynamic protrusions contribute to cell movement and interaction with the environment.