Cells are dynamic, moving entities, fundamental to life. This locomotion is orchestrated by specialized structures: lamellipodia and filopodia. These extensions allow cells to navigate complex environments and participate in many biological processes. Understanding how these cellular ‘feet’ operate provides insight into microscopic life.
Defining Lamellipodia and Filopodia
Lamellipodia are broad, sheet-like protrusions of the cell membrane at the leading edge of a migrating cell. They are thin, ranging from 0.1 to 0.3 micrometers in thickness and can extend several micrometers in length, appearing as veil-shaped extensions. These structures are largely devoid of major organelles, instead containing a dense, branched network of actin filaments that drives their expansion. Lamellipodia are associated with broad, sweeping movements, allowing cells to cover ground efficiently.
Filopodia, in contrast, are slender, finger-like projections that extend from the cell surface, protruding from or alongside lamellipodia. They are much thinner, 0.1 to 0.5 micrometers in diameter, but can extend up to 10 micrometers or more in length. Filopodia are composed of parallel bundles of actin filaments, providing them with a more rigid, antenna-like quality. Their primary function is probing the environment, sensing cues, and establishing initial contacts with the surrounding matrix or other cells.
How They Drive Cell Movement
Cell propulsion by lamellipodia and filopodia relies on the dynamic assembly and disassembly of actin filaments. At the leading edge, globular actin (G-actin) monomers are added to existing filamentous actin (F-actin) at their “barbed” ends, pushing the cell membrane forward. This continuous growth of the actin network generates the force for membrane protrusion.
In lamellipodia, this polymerization is facilitated by the Arp2/3 complex, which nucleates the formation of new branched actin filaments from existing ones, creating a dense meshwork. As the lamellipodium extends, new adhesion sites, involving integrin proteins, anchor the actin network to the underlying surface. This adhesion stabilizes the newly extended protrusion, allowing the cell to gain traction.
Following protrusion and adhesion, the cell body must be pulled forward. This step involves motor proteins, myosin II. Myosin II binds to actin filaments within the cell and uses energy from ATP hydrolysis to generate contractile forces. This contraction at the rear of the cell, involving stress fibers and focal adhesions, pulls the cell body forward and facilitates the detachment of older adhesions, completing the cycle of movement. The coordinated interplay of actin polymerization at the front and myosin-driven contraction at the rear allows for continuous cellular migration.
Their Role in Biological Processes
Lamellipodia and filopodia are instrumental in a wide array of biological processes. In embryonic development, these structures guide cell migration. For instance, filopodia can extend over hundreds of micrometers to establish intercellular bridges and transport signaling molecules, guiding cells to their correct positions. The precise control of cell movement during embryogenesis ensures that complex structures, such as the nervous system, develop correctly.
During wound healing, fibroblasts and keratinocytes at the wound margin extend lamellipodia and filopodia to close the injury. Lamellipodia facilitate the broad, crawling movement of cells, while filopodia can sense the wound environment and even “zipper” together with filopodia from neighboring cells to mechanically close the wound. This coordinated action is important for tissue repair and regeneration.
The immune response also relies on the migratory capabilities of cells driven by these protrusions. Immune cells, such as macrophages and T cells, use lamellipodia and filopodia to navigate through tissues and reach sites of infection or inflammation. Filopodia act as sensory antennae, allowing immune cells to detect chemical cues and efficiently target pathogens or damaged cells. This directed migration is important to the body’s defense mechanisms.
In cancer metastasis, lamellipodia and filopodia play a role in disease spread. Cancer cells often exhibit increased numbers and activity of these protrusions, enabling them to invade surrounding healthy tissues and disseminate throughout the body. By forming these dynamic extensions, cancer cells can navigate complex extracellular matrices, enter the bloodstream, and establish secondary tumors in distant organs, making these structures potential targets for therapeutic interventions.