Actin Dynamics in Cell Migration Mechanisms

Cell migration is driven by the dynamic remodelling of the actin cytoskeleton, which underpins processes ranging from embryonic development and immune surveillance to wound healing and metastasis. Central to this remodelling are branched and linear actin networks that power protrusive structures—lamellipodia and filopodia—at the leading edge, while contractile actomyosin bundles facilitate cell body translocation and retraction. Initiation of protrusion is governed by Rho family GTPases, which activate nucleation factors such as the Arp2/3 complex and formin family proteins to generate new filaments. Coordinated assembly and disassembly of these filaments are finely tuned by regulatory complexes—including WAVE/Scar, Ena/VASP and FHOD/FMNL formins—and by mechanical feedback from focal adhesions that link cytoskeletal forces to the extracellular matrix. In diverse three-dimensional environments, cells adopt versatile modes of migration, switching between mesenchymal and amoeboid behaviours in response to matrix architecture and chemical cues. Dysregulation of actin dynamics contributes to developmental disorders, immunodeficiencies and cancer cell invasion, highlighting the global significance of understanding the molecular circuitry that governs actin remodelling during migration.

Research from Nature Portfolio

Recent studies have identified a novel regulatory circuit centred on a phosphatase scaffold that associates with an alternative WAVE complex at the lamellipodial edge, revealing a mechanism by which actin branching and protrusion persistence are controlled. Foundational work has further demonstrated that transient organisation of stress fibres and upregulation of Ena/VASP-like proteins contribute to cell stiffening prior to malignant transformation, emphasising the mechanical interplay between polymerisation and contractility. Additional investigations have shown that FMNL formin family members cooperate with Arp2/3-dependent networks to generate the force required for lamellipodial protrusion, establishing formins as critical amplifiers of protrusive power in migrating cells.

Actin Dynamics in Cell Migration Mechanisms publication trend

The graph below shows the total number of articles in actin dynamics in cell migration mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Actin polymerization: Process by which globular actin monomers assemble into filamentous actin (F-actin) structures.

Lamellipodium: Broad, sheet-like protrusion at the leading edge of a migrating cell composed of a branched actin network.

Filopodium: Thin, finger-like projection containing parallel bundles of actin filaments, often involved in environmental sensing.

Arp2/3 complex: Heptameric protein assembly that nucleates new actin branches from the sides of existing filaments.

Formins: Family of proteins that nucleate and elongate unbranched actin filaments, contributing to linear bundle formation.

WAVE regulatory complex: Multi-subunit assembly that, upon activation by Rac GTPase, stimulates Arp2/3-mediated actin branching.

Focal adhesion: Dynamic multi-protein assembly linking the actin cytoskeleton to the extracellular matrix through integrin receptors.

References

1. PPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex. Nature Communications (2023).
2. Actin stress fiber organization promotes cell stiffening and proliferation of pre-invasive breast cancer cells. Nature Communications (2017).
3. FMNL formins boost lamellipodial force generation. Nature Communications (2017).
4. GSK3 and lamellipodin balance lamellipodial protrusions and focal adhesion maturation in mouse neural crest migration. Cell Reports (2023).
5. Upregulation of ENAH by a PI3K/AKT/β-catenin cascade promotes oral cancer cell migration and growth via an ITGB5/Src axis. Cellular & Molecular Biology Letters (2024).
6. Orchestration of synaptic functions by WAVE regulatory complex-mediated actin reorganization. Experimental & Molecular Medicine (2023).