Cell migration depends on dynamic remodeling of the actin cytoskeleton and microtubules. At the leading edge, Arp2/3 complex nucleates actin polymerization, creating branched filaments that polymerize against the membrane, generating lamellipodial protrusions. Myosin-II motors in the cell body contract actin bundles (stress fibers), generating pulling force. Focal adhesions link the cytoskeleton to the extracellular matrix through integrin receptors. Cells sense extracellular gradients (chemokines, matrix stiffness, adhesion ligands) and migrate toward or away from signals, fundamental to development, immunity, and wound healing.
From your understanding of eukaryotic cell compartmentalization, you know that cells have an internal cytoskeleton that provides structural support and organizes the interior. Cell migration takes this further: the cytoskeleton is not just scaffolding — it is a dynamic engine that can propel the entire cell forward. The process is remarkably coordinated, involving simultaneous construction at the front, contraction in the middle, and disassembly at the rear.
The cycle of migration has four repeating steps. First, the cell extends a flat, sheet-like protrusion called a lamellipodium at its leading edge. This is driven by actin polymerization: the Arp2/3 complex (activated by signals from the cell surface) nucleates new actin filaments that branch off existing ones at 70° angles, creating a dense, pushing meshwork. As actin monomers add to filament ends pressed against the membrane, they generate a mechanical force that physically pushes the membrane forward — no motor protein is needed for this step, just the thermodynamics of polymerization. Second, the newly extended membrane must attach to the surface it is crawling on. New focal adhesions form as integrin receptors in the extended lamellipodium engage extracellular matrix proteins, creating anchor points.
Third, the cell body must follow the leading edge. This is where myosin-II motors come in. Myosin-II assembles into bipolar filaments that slide along actin stress fibers — bundled, contractile actin cables that run through the cell body — generating a squeezing force that pulls the bulk of the cell forward. Think of the leading edge as a hand reaching forward to grab a handhold, and myosin contraction as the arm pulling the body up to meet the hand. Fourth, adhesions at the trailing edge must release, and the rear of the cell must retract. This involves disassembly of old focal adhesions and myosin-powered contraction that snaps the tail forward.
What makes migration purposeful rather than random is directional sensing. Cells detect shallow gradients of chemical signals (chemotaxis), substrate stiffness (durotaxis), or adhesion molecule density (haptotaxis) and preferentially extend lamellipodia toward the signal source. Small GTPases — particularly Rac1 at the leading edge (promoting Arp2/3 activation and actin branching) and RhoA at the rear (promoting myosin contraction and tail retraction) — create front-rear polarity. This polarity ensures the cell moves in one direction rather than extending protrusions everywhere at once. Cell migration is essential throughout life: neutrophils chase bacterial signals to sites of infection, fibroblasts migrate into wounds to deposit new matrix, and during embryonic development, neural crest cells migrate enormous distances to form structures ranging from facial bones to the enteric nervous system.