Filopodia, formed by migrating growth cones of neurons and some types of fibroblasts, are essentially one-dimensional. They contain a core of long, bundled actin filaments, which are reminiscent of those in microvilli but longer and thinner, as well as more dynamic. Lamellipodia, formed by epithelial cells and fibroblasts, as well as by some neurons, are two-dimensional, sheetlike structures. They contain a cross-linked mesh of actin filaments, most of which lie in a plane parallel to the solid substratum. Invadopodia and related structures known as podosomes represent a third type of actin-rich protrusion. These extend in three dimensions and are important for cells to cross tissue barriers, as when a metastatic cancer cell invades the surrounding tissue. Invadopodia contain many of the same actin-regulatory components as filopodia and lamellipodia, and they also degrade the extracellular matrix, which requires the delivery of vesicles containing matrix-degrading proteases.
A distinct form of membrane protrusion called blebbing is often observed in vivo or when cells are cultured on a pliable extracellular matrix substratum. Blebs form when the plasma membrane detaches locally from the underlying actin cortex, thereby allowing cytoplasmic flow to push the membrane outward (Figure 16–76). Bleb formation also depends on hydrostatic pressure within the cell, which is generated by the contraction of actin and myosin assemblies. Once blebs have extended, actin filaments reassemble on the bleb membrane to form a new
Figure 16–76 Membrane bleb induced by disruption of the actin cortex. On the left is a light micrograph showing a spherical membrane protrusion or bleb induced by laser ablation of a small region of the actin cortex. The cortex is labeled green in the middle image by expression of GFP-actin. (Courtesy of Ewa Paluch.) actin cortex. Recruitment of myosin II and contraction of actin and myosin can then power retraction of membrane blebs. Alternatively, extension of new blebs from old ones can drive cell migration.
Lamellipodia Contain All of the Machinery Required for Cell Motility
Lamellipodia have been particularly well studied in the epithelial cells of the epidermis of fish and frogs; these epithelial cells are known as keratocytes because of their abundant keratin filaments. These cells normally cover the animal by forming an epithelial sheet, and they are specialized to close wounds very rapidly, moving at rates of up to 30 μm/min. When cultured as individual cells, keratocytes assume a distinctive shape with a very large lamellipodium and a small, trailing cell body that is not attached to the substratum (Figure 16–77). Fragments of this lamellipodium can be sliced off with a micropipette. Although the fragments generally lack microtubules and membrane-enclosed organelles, they continue to crawl normally, looking like tiny keratocytes.
The dynamic behavior of actin filaments in keratocyte lamellipodia can be studied by labeling a small patch of actin and examining its fate. This reveals that, while the lamellipodia crawl forward, the actin filaments remain stationary with respect to the substratum. The actin filaments in the meshwork are mostly oriented with their plus ends facing forward. The minus ends are frequently attached to the sides of other actin filaments by Arp 2/3 complexes (see Figure 16–16), helping to form the two-dimensional web (Figure 16–78). The web as a whole is undergoing treadmilling, assembling at the front and disassembling at the back, reminiscent of the treadmilling that occurs in individual actin filaments discussed previously (see Figure 16–14).