Many cells move by crawling over surfaces rather than by using cilia or flagella to swim. Predatory amoebae crawl continuously in search of food, and they can easily be observed to attack and devour smaller ciliates and flagellates in a drop of pond water (see Movie 1.4). In animals, almost all cell locomotion occurs by crawling, with the notable exception of swimming sperm. During embryogenesis, the structure of an animal is created by the migrations of individual cells to specific target locations and by the coordinated movements of whole epithelial sheets (discussed in Chapter 21). In vertebrates, neural crest cells are remarkable for their long-distance migrations from their site of origin in the neural tube to a variety of sites throughout the embryo (see Movie 21.5). Long-distance crawling is fundamental to the construction of the entire nervous system: it is in this way that the actin-rich growth cones at the advancing tips of developing axons travel to their eventual synaptic targets, guided by combinations of soluble signals and signals bound to cell surfaces and extracellular matrix along the way.
The adult animal also seethes with crawling cells. Macrophages and neutrophils crawl to sites of infection and engulf foreign invaders as a critical part of the innate immune response. Osteoclasts tunnel into bone, forming channels that are filled in by the osteoblasts that follow after them, in a continuous process of bone remodeling and renewal. Similarly, fibroblasts migrate through connective tissues, remodeling them where necessary and helping to rebuild damaged structures at sites of injury. In an ordered procession, the cells in the epithelial lining of the intestine travel up the sides of the intestinal villi, replacing absorptive cells lost at the tip of the villus. Unfortunately, cell crawling also has a role in many cancers, when cells in a primary tumor invade neighboring tissues and crawl into blood vessels or lymph vessels and then emerge at other sites in the body to form metastases.
Cell migration is a complex process that depends on the actin-rich cortex beneath the plasma membrane. Three distinct activities are involved: protrusion, in which the plasma membrane is pushed out at the front of the cell; attachment, in which the actin cytoskeleton connects across the plasma membrane to the substratum; and traction, in which the bulk of the trailing cytoplasm is drawn forward (Figure 16–75). In some crawling cells, such as keratocytes from the fish epidermis, these activities occur simultaneously, and the cells seem to glide forward smoothly without changing shape. In other cells, such as fibroblasts, these activities are more independent, and the locomotion is jerky and irregular.
The first step in locomotion, protrusion of a leading edge, frequently relies on forces generated by actin polymerization pushing the plasma membrane outward. Different cell types generate different types of protrusive structures, including filopodia (also known as microspikes) and lamellipodia. These are filled with dense cores of filamentous actin, which excludes membrane-enclosed organelles. The structures differ primarily in the way in which the actin is organized by actin-cross-linking proteins (see Figure 16–22).
movement of unpolymerized actin
Figure 16–75 A model of how forces generated in the actin-rich cortex move a cell forward. The actin-polymerizationdependent protrusion and firm attachment of a lamellipodium at the leading edge of the cell move the edge forward (green arrows at front) and stretch the actin cortex. Contraction at the rear of the cell propels the body of the cell forward (green arrow at back) to relax some of the tension (traction). New focal contacts are made at the front, and old ones are disassembled at the back as the cell crawls forward. The same cycle can be repeated, moving the cell forward in a stepwise fashion. Alternatively, all steps can be tightly coordinated, moving the cell forward smoothly. The newly polymerized cortical actin is shown in red.