Cell Polarization and Migration

Cell migration is the movement of cells from one place to another. It is important in embryological development, repair and regeneration, immune response, and metastasis. Cells respond to chemical signals or mechanical signals from specific organs or tissues.

The movement process has three main steps: polarization, protrusion, and release. During polarization, the cell forms a clear front and rear, which sets the direction of movement. Then the front protrudes, forms new adhesions, and creates...

Actin filaments help cells move, divide, and take in material from outside the cell. Actin is a family of globular proteins that is very abundant in eukaryotic cells. It makes up about 1 to 5 percent of total cell protein concentration.

Actin monomers can join together to form a polarized network called the actin cytoskeleton. This network creates pushing, pulling, and resistance forces that support cell migration. Cell movement often follows repeated steps of front-edge protrusion, attachment...

Cell surface protrusions help cells move, absorb nutrients, and respond to their surroundings. These extensions form when the cytoskeleton, the cell’s internal support system, rearranges. The most commonly seen protrusions include lamellipodia, pseudopodia, filopodia, microvilli, invadopodia, and podosomes.

These protrusions are often grouped as static or dynamic. Microvilli are stable, finger-like projections with a generally stable actin architecture. They are brush-like extensions on the...

Cells move forward by building lamellipodia, which are thin membrane protrusions at the leading edge. These structures are supported by a mesh of actin filaments that may be linked, branched, or unbranched. Actin works with myosin motor proteins to form the actomyosin complex in the cytoskeleton, and this complex can generate contractile stress. That contractility helps cells sense the stiffness of the extracellular matrix, or ECM, and apply force during migration.

Lamellipodia begin to form...

Filopodia are thin, actin-rich cell protrusions that help cells move and make contact. They appear in different cell types in different places and lengths. That variation suggests they can support several cell functions.

In many cases, filopodia guide migrating cells during normal tissue morphogenesis and cancer metastasis. They help cells recognize the extracellular matrix and make their first contact with it. Filopodia can also act as stationary anchors or help two cells communicate.

A...

Invadopodia are cell surface structures that help cancer cells break down the extracellular matrix, or ECM. The ECM is the material outside cells that gives tissues support. Invadopodia are part of a larger group called invadosomes, which also includes structures found in normal cells such as macrophages, endothelial cells, and neurons.

Macrophage podosomes and tumor cell invadopodia are both invadosomes, but they are not the same. Podosomes are short-lived and last only a few minutes.

Blebbing is a membrane change seen in cell movement and cell death. A bleb is a membrane protrusion that forms when pressure from the cytoplasm pushes the plasma membrane outward. Blebs can appear in fibroblasts, immune cells, and single-celled organisms such as amoebas.

Blebs help cells move through tight spaces in the extracellular matrix, or ECM. In multicellular organisms, migrating cells must squeeze between other cells and through this three-dimensional matrix. Actin-driven protrusions...

Myosin is a motor protein that helps cells migrate by building force, strengthening attachments, and setting cell polarity. In animal cells, myosin II is the most common type. It binds and cross-links actin filaments, the protein fibers that help a cell move and change shape.

Myosin II is a hexamer, or six-part complex. It has two heavy chains with globular heads and coiled-coil tails, plus two regulatory light chains and two essential light chains. The ATPase sites on the myosin heads break...

Cell polarity gives a cell two different sides. This uneven layout is important for embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. In migrating cells, signals from inside or outside the cell trigger pathways that reorganize the actin cytoskeleton and build this polarity.

The Rho family proteins Cdc42, Rac, and Rho help control that process. These proteins are small GTPases, which means they act like molecular switches and can shift...

Cells follow chemical gradients by sensing cues in their environment and changing their cytoskeleton to move toward or away from them. This directional movement is called chemotaxis. It helps guide many processes, including embryogenesis, development, immune response, tissue repair and regeneration, and reproduction.

Chemical signals can act as attractants or repellents. In axon development, for example, chemoattractants and chemorepellents help direct a growing axon toward the correct target.

Cell polarity during migration depends on the cytoskeleton. As a cell moves, it changes shape through repeated attachment to and detachment from the substratum, the surface it grows or moves on. The cell also shifts its organelles to match these changes.

This movement is controlled by a dynamic cytoskeletal network. The network includes actin filaments, intermediate filaments, and microtubules. These parts do not work alone. They communicate through cytoskeletal crosstalk, which means direct...