Cell movement, or cell motility, is a fundamental biological process underlying nearly every aspect of life, from embryonic formation to tissue repair. This motion is a highly coordinated, active function powered by the cell’s internal scaffolding, the cytoskeleton. Dynamic rearrangement of the cytoskeleton allows a cell to push, pull, and sense its environment to navigate complex biological landscapes. Lamellipodia and filopodia are two primary types of specialized, dynamic extensions of the cell membrane. These structures serve as the cell’s leading edge, enabling cells to explore their surroundings and propel the cell body forward.
Lamellipodia: The Broad Pushers
The lamellipodium is a broad, flat, thin protrusion that forms the primary engine for forward movement in a migrating cell. This sheet-like structure is typically 0.1 to 0.3 micrometers thick, extending up to five micrometers from the cell’s front edge. Lamellipodia are largely devoid of major organelles, featuring a dense, highly active internal network of actin filaments that drives the extension. The continuous assembly of actin filaments at the leading edge generates the sustained protrusive force needed to push the cell body forward. As the lamellipodium extends, it forms nascent adhesions with the underlying substrate, anchoring the cell via integrin-mediated adhesions. This dynamic process of protrusion, adhesion, and subsequent retraction of the cell’s rear is known as mesenchymal migration.
Filopodia: The Cellular Sensors
Filopodia are slender, spike-like projections that act as cellular antennae, distinct from the broad lamellipodium. These thin extensions typically measure between 0.1 and 0.3 micrometers in diameter and can extend several micrometers in length. Filopodia often emerge from the lamellipodium, projecting outward to explore the environment. Their primary role is environmental sensing and pathfinding, gathering information about chemical gradients and physical cues. Internally, filopodia are composed of long, parallel bundles of ten to thirty actin filaments. These filaments are rigidly cross-linked by proteins such as fascin, maintaining the stiff, finger-like shape necessary for probing. By sensing the extracellular matrix and other cells, filopodia determine the correct direction for migration, relaying this sensory input back to the lamellipodium.
The Mechanics of Actin Assembly
Both lamellipodia and filopodia are built from the same fundamental material: actin. Actin is a globular protein (G-actin) that polymerizes into long, fibrous polymers (F-actin). Specialized regulatory proteins dictate the difference in their appearance and function by controlling how these polymers are organized. The polymerization process, where G-actin monomers are rapidly added to the fast-growing barbed ends of F-actin filaments, is the source of the mechanical force that pushes the cell membrane outward.
Lamellipodium Architecture
The branched, sheet-like network characteristic of the lamellipodium is created by the Arp2/3 complex. This protein machine nucleates new actin filaments by binding to the side of an existing filament. It initiates the growth of a new “daughter” filament at a characteristic 70-degree angle. This repeated branching creates a dense, quasi-two-dimensional meshwork that generates a broad, uniform pushing force against the membrane.
Filopodium Architecture
In contrast, the long, parallel bundles of filopodia are formed by formins. Formins sit at the barbed end of an actin filament, facilitating the rapid, linear elongation by continually adding G-actin monomers. They also protect the growing end from being capped by other regulatory proteins, allowing the filament to grow into a long, unbranched structure. Multiple formin-driven filaments are then bundled together by cross-linking proteins like fascin to create the stiff, probing spike of the filopodium.
Biological Roles in Health and Disease
The precise coordination of lamellipodia and filopodia is indispensable for numerous physiological processes.
Development and Tissue Repair
During embryonic development, the movement of cell sheets and individual cells relies on these protrusions to correctly shape tissues and organs. For example, the formation of the nervous system is guided by filopodia on the tips of growing axons that sense guidance cues toward their target cells. Both structures also play a significant role in maintaining tissue integrity and wound healing. Fibroblasts and keratinocytes use lamellipodia to migrate into the wound site, while filopodia explore the damaged area to find chemical signals that direct the repair process.
Immune Function and Disease
Immune cells, such as macrophages and T-cells, use these dynamic extensions to navigate complex tissues and track down pathogens or sites of inflammation. Macrophages, for instance, use filopodia as “phagocytic tentacles” to capture targets for engulfment. The dysregulation of these cytoskeletal structures is a hallmark of certain disease states, particularly cancer. Cancer cells often hijack the molecular machinery of lamellipodia and filopodia to become highly migratory and invasive. By over-activating the signaling pathways that control Arp2/3 and formins, cancer cells generate excessive protrusive force. This enables them to breach tissue barriers and disseminate from a primary tumor, allowing metastasis to occur.