Cell Migration

Cell migration begins when a cell responds to an external polarizing chemical signal. This signal is detected by membrane receptors such as G-protein coupled receptors (GPCR) and receptor tyrosine kinase receptors (RTK). The detection causes an accumulation of phosphatidylinositol (3,4,5) triphosphate (PIP3) at the leading edge, initiating the migration process.

Cells extend a leading edge that attaches to the substrate via secreted adhesive compounds. The trailing edge also adheres to anchor the cell. Cytoskeletal motility structures then generate contractions that propel the cell toward its destination. Finally, the adhesive attachment at the trailing edge releases, and these steps repeat cyclically until the cell reaches its destination.

Chemokinesis occurs when signaling molecules stimulate cell migration without dictating directionality, allowing symmetric or asymmetric movement. Chemotaxis involves a gradient of soluble or substrate-bound signaling molecules that dictates the directionality of cellular movement. Both are types of responses initiated by different signaling molecules during cell polarization.

Rac and Cdc42 are Rho-family small proteins activated by PIP3 accumulation at the leading edge. They cause actin polymerization, generating protrusions at the leading edge. Rho, another Rho-family protein, causes actin-myosin contractions at the trailing edge, enabling the cell to propel itself forward during migration.

Lamellipodia are broad, sheet-like protrusions containing a branched network of thin, short actin filaments. They are found in fibroblasts, immune cells, and neurons. When lamellipodia lift away from the substrate and move backward, they create a distinctive ruffling movement that facilitates cell migration and exploration of the microenvironment.

Filopodia are thin, finger-like protrusions that emanate from cell membranes, unlike the broad sheet-like lamellipodia. They are often observed in neurons working alongside lamellipodia during migration. Both protrusion types vary in shape depending on how actin is assembled as a physical scaffold.

Cell migration is essential for proper development and viability of organisms throughout their life. When cells cannot migrate properly to their designated locations, various disorders occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis. Cell migration also occurs during embryogenesis cleavage and blastulation, when cells must reach specific positions to form tissues.