Actin Dynamics in Cellular Motility Mechanisms

Actin filaments generate the forces that drive cell movement, underpinning processes from embryonic morphogenesis and wound healing to immune surveillance and cancer metastasis. Polymerisation of globular actin into filamentous networks at the leading edge produces protrusive lamellipodia and filopodia, while coordinated depolymerisation and severing at the rear enable retraction and turnover. The interplay of nucleators such as the Arp2/3 complex and formins with accessory factors including capping protein, twinfilin and cortactin establishes diverse filament architectures suited to distinct motile behaviours. Actin assemblies also transduce mechanical signals from the extracellular matrix, with network viscoelasticity and filament flow contributing to stiffness sensing and traction force generation. Advances in high-resolution imaging and biophysical modelling have begun to reveal how these dynamic cycles of assembly and disassembly are tuned to produce rapid, adaptable cellular motility across physiological and pathological contexts.

Research from Nature Portfolio

Recent studies have elucidated how barbed-end regulators integrate to fine-tune filament assembly. Multicolour single-molecule imaging demonstrated that formin, capping protein and twinfilin form transient trimeric complexes at the barbed end, whereby twinfilin displaces capping protein to promote processive formin-driven elongation. Structural analysis using cryo-electron microscopy has revealed that cortactin binds activated Arp3 at the branch junction, stabilising the daughter filament by reinforcing the interface between Arp2/3 and the first actin subunit, thereby contributing to the persistence of branched networks under mechanical load. In parallel, advanced mechanical and live-cell assays have shown that in fibroblasts, stiffness-dependent traction can be generated independently of myosin by flowing actin networks; formin-driven polymerisation and Arp2/3-nucleated branches mechanically reinforce the viscoelastic F-actin to transmit extracellular matrix cues, underpinning a new model of force transduction based on network rheology.

Actin Dynamics in Cellular Motility Mechanisms publication trend

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

Technical terms

Arp2/3 complex: heptameric protein assembly that nucleates branched actin filaments from existing filaments.

Barbed end: the rapidly growing terminus of an actin filament where monomer addition occurs.

Formin: a processive actin nucleator that binds barbed ends to promote filament elongation.

Capping protein: a heterodimer that binds filament barbed ends to arrest polymerisation.

Twinfilin: a depolymerisation factor that regulates barbed-end dynamics and modulates elongation.

Cortactin: an actin-binding protein that stabilises Arp2/3-nucleated branches by reinforcing filament interfaces.

Viscoelasticity: the property of actin networks to display both fluid and elastic mechanical responses.

References

1. Multicomponent regulation of actin barbed end assembly by twinfilin, formin and capping protein. Nature Communications (2023).
2. Cortactin stabilizes actin branches by bridging activated Arp2/3 to its nucleated actin filament. Nature Structural & Molecular Biology (2024).
3. Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin. Communications Materials (2024).
4. Regeneration of actin filament branches from the same Arp2/3 complex. Science Advances (2024).
5. WH2 and proline‐rich domains of WASP‐family proteins collaborate to accelerate actin filament elongation. The EMBO Journal (2017).