Actin Dynamics in Cell Migration and Wound Healing

The orchestrated remodelling of the actin cytoskeleton lies at the heart of cell migration and the complex biology of wound repair. Actin filaments undergo rapid polymerisation and depolymerisation to generate protrusive structures—lamellipodia and filopodia—that drive motile cells forward. At the leading edge, polymerising actin networks push the plasma membrane outward, while adhesive contacts between the cytoskeleton and extracellular matrix transmit traction forces. Inside the wound milieu, migrating keratinocytes, fibroblasts and endothelial cells coordinate through gradients of chemical and mechanical signals to re-epithelialise the surface, deposit extracellular matrix and establish new vasculature. Regulators of actin dynamics—including the Arp2/3 complex, formins, cofilin and profilin—are integrated by small GTPases such as Rac1 and RhoA, which control lamellipodial extension, myosin-driven contractility and focal adhesion assembly and disassembly. The balance of protrusive and contractile forces not only governs directional motility but also influences the inflammatory response and matrix remodelling essential for timely closure of tissue defects. Dysregulation of these processes can result in chronic non-healing wounds or, conversely, excessive scar formation. Understanding the molecular choreography of actin dynamics offers routes to novel therapies that might enhance regenerative capacity or restrain pathological scarring.

Research from Nature Portfolio

Recent studies have shown that distinct guanine nucleotide exchange factors bias Rac1 towards divergent migratory programmes by altering its interactome. In particular, one factor promotes anti-migratory signalling, while another enhances binding between Rac1 and the actin-remodelling protein Flightless I to drive cell contraction independently of the RhoA–ROCK axis. This finding reveals a nuanced mechanism by which cancer cells or wound-reparative cells may fine-tune protrusion and adhesion turnover. In a separate model of intestinal mucosal injury, investigators have demonstrated that high levels of Flightless I amplify pro-inflammatory cytokine production, inhibit Wnt/β-catenin signalling and impair crypt regeneration. Conversely, reduction of Flightless I accelerates mucosal repair, attenuates inflammation and restores epithelial architecture, underscoring its dual role as an actin regulator and immuno-modulator in tissue healing.

Actin Dynamics in Cell Migration and Wound Healing publication trend

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

Technical terms

Actin cytoskeleton: A dynamic network of filamentous (F-actin) and monomeric (G-actin) proteins that provides structural support and drives cell movement.

Lamellipodium: Broad, sheet-like cellular protrusion formed by a branched actin meshwork at the leading edge of migrating cells.

Focal adhesion: Multi-protein complexes that couple the actin cytoskeleton to extracellular matrix ligands via integrins, transmitting traction and signalling cues.

Small GTPase: A family of molecular switches (e.g. Rac1, RhoA) that cycle between active and inactive forms to regulate actin dynamics and cell morphology.

Flightless I: An actin-binding protein of the gelsolin family that modulates filament assembly, gene transcription and inflammatory signalling in tissue repair.

YAP1: A transcriptional co-activator in the Hippo pathway that senses cytoskeletal tension and regulates genes involved in proliferation and differentiation.

References

1. FLII Modulates the Myogenic Differentiation of Progenitor Cells via Actin Remodeling-Mediated YAP1 Regulation. International Journal of Molecular Sciences (2023).
2. Differential Rac1 signalling by guanine nucleotide exchange factors implicates FLII in regulating Rac1-driven cell migration. Nature Communications (2016).
3. Multifunctional Roles of the Actin-Binding Protein Flightless I in Inflammation, Cancer and Wound Healing. Frontiers in Cell and Developmental Biology (2020).
4. Flightless I exacerbation of inflammatory responses contributes to increased colonic damage in a mouse model of dextran sulphate sodium-induced ulcerative colitis. Scientific Reports (2019).
5. Actin‐Tethered Junctional Complexes in Angiogenesis and Lymphangiogenesis in Association with Vascular Endothelial Growth Factor. BioMed Research International (2015).