Role of Myosin in Cell Migration

Myosin-II is a motor protein with globular head regions that bind filamentous actin. These heads use energy from ATP hydrolysis to pull and contract actin bundles. This myosin-driven contraction generates the mechanical forces that extend membrane protrusions at the cell's leading edge and retract the membrane at the trailing edge, pushing the cell forward during migration.

At the lamellipodial front, myosin contracts actin filaments anchored to cell-matrix junctions, increasing mechanical stress and strengthening these junctions into mature focal adhesions. These anchorage points produce traction forces on the substratum. Myosin may also cluster adhesion molecules through actin bundling and alter linker protein conformations, exposing cryptic binding sites that further strengthen adhesions.

At the rear of the lamellipodium, bipolar myosin binds actin and bridges branched filaments. The myosin heads pull actin filaments and reorient them parallel to the lamellipodial front, retracting the sides of the cell. This retraction directs the rear of the cell to follow the leading edge, resulting in directed cell migration.

Myosin-II is a hexamer comprising two heavy chains with globular heads and coiled-coil tails, plus two regulatory and two essential light chains. The ATPase sites on the myosin heads hydrolyze ATP, and the released phosphate generates the force for contraction. This structure enables myosin to bind and cross-link actin filaments, driving cellular contraction and migration.

Myosin is essential for repositioning organelles, including the nucleus, Golgi apparatus, and centrosomes, in alignment with the cell's polarity. Myosin anchors actin filaments around the nucleus by interacting with the linker protein nesprin embedded in the nuclear membrane. This repositioning helps establish the cell front and rear necessary for directed migration.

Myosin-driven contraction of actin filaments and bundles generates the mechanical forces that drive cell migration. These contractile forces strengthen focal adhesions, produce traction forces on the substratum, and coordinate the retraction of the trailing edge. Without myosin contraction, cells cannot generate the organized forces needed for directed movement and proper cytoskeletal coordination in cell migration.

Two main mechanisms strengthen focal adhesions: myosin contractile force changes the conformation of cytoskeletal linker proteins like talin, exposing cryptic binding sites to actin and other proteins; and myosin-driven bundling of actin filaments clusters adhesion molecules such as integrins. Both mechanisms enhance adhesion maturation, enabling cells to generate sufficient traction forces for forward movement.