Cell Migration Mechanisms in Complex Environments

Cell migration underpins fundamental processes from embryonic development and immune surveillance to cancer metastasis and tissue repair. In vivo, cells navigate intricate landscapes comprising three-dimensional networks of extracellular matrix fibres, biochemical gradients and mechanical constraints. At the leading edge, dynamic protrusive structures—filopodia and lamellipodia—probe the environment, with actin polymerisation driving membrane extension. Traction force is generated through integrin-based adhesions that link the cytoskeleton to matrix ligands; subsequent actomyosin contractility propels the cell body forward while nucleus translocation is orchestrated by mechanosensitive elements. Matrix remodelling by proteases such as matrix metalloproteinases facilitates passage through dense networks, whereas physical parameters like fibre alignment, pore size and stiffness bias migration modes. Recent theoretical and experimental frameworks have begun to integrate these subprocesses, revealing how energy landscapes of bending, adhesion and contractility shape migratory paths. Understanding this multiscale interplay is crucial for designing biomaterials that guide cell behaviour and for developing interventions to inhibit aberrant migration in disease.

Research from Nature Portfolio

Experimental and theoretical approaches have elucidated how membrane protrusions coil around extracellular fibres of varying geometry. A biophysical model coupling curved membrane proteins and actin polymerisation predicts coiling on cylindrical fibres and cessation on flattened ones, a phenomenon confirmed by light-sheet microscopy. This work offers a unified framework linking bending and adhesion energies to protrusion orientation. In parallel, quantitative studies of three-dimensional collagen matrices have demonstrated that fibre alignment, rather than bulk stiffness or density alone, dictates cell motility. By systematically varying matrix microstructure, researchers showed that aligned fibres guide protrusion orientation, modulate matrix metalloproteinase activity and yield biphasic migration responses not foreseen by two-dimensional models. Together, these findings integrate physical and biochemical factors to predict migratory behaviour in complex fibrous environments.

Cell Migration Mechanisms in Complex Environments publication trend

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

Technical terms

Filopodia: Slender, actin-rich protrusions that sense environmental cues and guide migration.

Lamellipodia: Broad, sheet-like actin structures driving membrane extension at the leading edge.

Focal adhesions: Dynamic multi-protein complexes that anchor the cytoskeleton to the extracellular matrix through integrins.

Matrix metalloproteinases (MMPs): Enzymes that degrade extracellular matrix components, facilitating migration through dense tissues.

Actomyosin contractility: Force generation by myosin motors interacting with actin filaments, crucial for cell body translocation.

References

1. Experimental and theoretical model for the origin of coiling of cellular protrusions around fibers. Nature Communications (2023).
2. Three-dimensional matrix fiber alignment modulates cell migration and MT1-MMP utility by spatially and temporally directing protrusions. Scientific Reports (2015).
3. Actin Filaments Couple the Protrusive Tips to the Nucleus through the I‐BAR Domain Protein IRSp53 during the Migration of Cells on 1D Fibers. Advanced Science (2023).
4. Microtubules Disruption Alters the Cellular Structures and Mechanics Depending on Underlying Chemical Cues. Small (2024).
5. Adhesion tunes speed and persistence by coordinating protrusions and extracellular matrix remodeling. Developmental Cell (2023).