Cell Motility Mechanisms in Immune Responses

Immune surveillance and effective host defence depend on the capacity of leukocytes and antigen-presenting cells to migrate through complex tissue environments. At the core of this migration lies dynamic remodelling of the actin cytoskeleton, which generates protrusive forces at the leading edge and contractile forces at the rear. Cells interpret chemical cues such as chemokines via surface receptors to induce directed migration or chemotaxis, while adhesion receptors mediate traction on extracellular matrices. Beyond biochemical guidance, recent studies reveal that immune cells also sense physical properties of their surroundings—including membrane curvature and nuclear confinement—to fine-tune their migratory behaviour. These coordinated mechanisms ensure rapid patrolling of tissues, efficient homing to lymphoid organs and precise arrest at sites of infection or injury. Dysregulation of motility pathways can impair pathogen clearance or contribute to inflammatory disorders, underscoring the clinical relevance of understanding immune cell movement.

Research from Nature Portfolio

Recent studies have identified a shape-sensing axis in dendritic cells whereby mechanical deformation of the nuclear envelope triggers increased expression of key chemokine receptors, thereby enhancing steady-state migration to lymph nodes. This mechanism is mediated by a lipid enzyme and fine-tuned by local actin nucleation complexes, linking physical forces to transcriptional programmes that influence immune regulation. Another investigation has uncovered a curvature-sensitive machinery in immune-like cells: BAR-domain proteins that detect inward plasma membrane curvature locally inhibit actin polymerisation, enabling cells to decide whether to push forward or turn away when encountering obstacles. A foundational work further demonstrated that perinuclear actin assembly driven by the Arp2/3 complex disrupts the nuclear lamina to permit rapid passage through narrow constrictions, a process essential for leukocyte transit in dense tissues.

Cell Motility Mechanisms in Immune Responses publication trend

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

Technical terms

Actin polymerisation: Assembly of globular actin monomers into filamentous networks that generate protrusive force.

Arp2/3 complex: A protein assembly that nucleates branched actin filaments, critical for lamellipodial and perinuclear actin networks.

BAR-domain protein: A curvature-sensing module that binds to specific membrane shapes and regulates cytoskeletal dynamics.

Chemotaxis: Directed movement of cells along a gradient of soluble chemical cues.

Chemokine receptor: A G-protein-coupled receptor that recognises chemokines to guide cell migration.

Microfluidics: Technology that manipulates small volumes of fluids in micro-scale channels, used to assay single-cell behaviour.

Nuclear lamina: A fibrous network beneath the inner nuclear membrane that contributes to nuclear stiffness and shape maintenance.

References

1. Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes. Nature Immunology (2024).
2. Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles. Nature Communications (2023).
3. Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments. Nature Communications (2016).
4. A Bidirectional Single‐Cell Migration and Retrieval Chip for Quantitative Study of Dendritic Cell Migration. Advanced Science (2023).
5. Microtubules control cellular shape and coherence in amoeboid migrating cells. Journal of Cell Biology (2020).
6. Actin-Based Cell Protrusion in a 3D Matrix. Trends in Cell Biology (2018).