Actin Dynamics in Cellular Mechanics

Actin dynamics underlie the mechanical behaviour of eukaryotic cells by driving shape changes, migration and division. Monomeric actin (G-actin) polymerises into filamentous actin (F-actin) in a process governed by nucleation, elongation and turnover. The barbed end of the filament favours rapid monomer addition, whereas the pointed end typically mediates slower disassembly. Cellular regulators such as the Arp2/3 complex and formins nucleate and shape branched or linear networks, while severing factors like cofilin accelerate depolymerisation. Crosslinking proteins organise these filaments into higher-order architectures, tuning network stiffness and contractility. Together, these dynamic processes convert chemical energy into mechanical work, underpinning tissue morphogenesis, immune function and mechanotransduction. Dysregulation of actin turnover is implicated in developmental disorders, metastasis and myopathies, emphasising the global significance of actin mechanics in health and disease.

Research from Nature Portfolio

High-resolution cryo-EM studies of the F-actin pointed end have revealed the structural basis for filament stabilisation and disassembly. In the absence of stabilising ligands, the two terminal subunits adopt a twisted conformation that predisposes the pointed end to depolymerisation. Binding of small molecules such as phalloidin flattens this region, preventing subunit loss, while DNase I can bind cooperatively to destabilise terminal contacts and promote disassembly. Complementary work has elucidated how inorganic phosphate is released from both the core and barbed end of actin filaments via a transient ‘molecular backdoor’. This backdoor remains open at the barbed end to allow rapid phosphate escape, but is predominantly closed within the filament core, opening only through concerted amino acid rearrangements. Mutations associated with nemaline myopathy bias the backdoor toward an open state, accelerating phosphate release and shortening the ADP-Pi cap, thereby linking atomic structure to disease-related filament dynamics.

Actin Dynamics in Cellular Mechanics publication trend

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

Technical terms

F-actin: filamentous polymer of actin subunits responsible for cytoskeletal structure and force generation.

G-actin: globular monomeric form of actin that assembles into filaments.

Barbed end: rapidly growing end of an actin filament where monomer addition predominates.

Pointed end: slower-growing end of an actin filament where monomer dissociation is favoured.

Nucleation: initiation step in filament formation requiring specialised factors to stabilise actin subunit oligomers.

Arp2/3 complex: seven-subunit nucleator that induces branched networks of actin filaments.

Formin: family of proteins that processively elongate unbranched actin filaments at their barbed ends.

Cofilin: actin-binding protein that promotes filament severing and disassembly by altering subunit conformation.

Crosslinker: protein that binds multiple filaments to organise higher-order actin networks.

References

1. Phalloidin and DNase I-bound F-actin pointed end structures reveal principles of filament stabilization and disassembly. Nature Communications (2024).
2. Molecular mechanisms of inorganic-phosphate release from the core and barbed end of actin filaments. Nature Structural & Molecular Biology (2023).
3. Structural insights into actin filament turnover. Trends in Cell Biology (2025).
4. Fascin-induced bundling protects actin filaments from disassembly by cofilin. Journal of Cell Biology (2024).
5. The actin cortex at a glance. Journal of Cell Science (2018).