Shellard-and-Mayor-2020

Directional Cell Migration Overview

• Definition: Directional cell migration is guided by various external signals (chemical, mechanical, electrical) that dictate cell movement direction.

• Key Concepts:

  • Directional migration relies on responses to localized stimuli, often arranged in gradients.

  • Major pathways involve small GTPases and the actin cytoskeleton, suggesting common regulatory mechanisms across different stimuli.

Categories of Directional Cues

• Types of Cues:

  • Chemotaxis: Movement in response to soluble chemical gradients.

  • Galvanotaxis: Migration influenced by electric fields.

  • Haptotaxis: Directional migration along gradients of adhesion sites or immobilized signals.

  • Durotaxis: Movement directed by gradients in substrate stiffness.

Mechanisms of Cell Migration

Principles of Migration

• Cell Polarization: Essential for directional movement, involving actin polymerization at the leading edge.

• Force Generation:

  • Focal contacts anchor the front while stress fibers promote movement due to traction forces.

Chemical Gradient Formation

• Chemotactic Gradients:

  • Established by a source (producing attractants) and sink (removing them). Gradients drive cells towards higher concentrations.

  • Cells can self-generate gradients through degradation and diffusion mechanisms.

Mechanical and Structural Gradients

• Durotactic Gradients:

  • Stiffness gradients affect migration; cells can modify surrounding tissue stiffness through ECM interactions.

• Haptotactic Gradients:

  • Cells respond to gradients of adhesive substrates, which can be influenced by both secreted factors and local ECM constituents.

Electrical Gradients

• Galvanotaxis:

  • Electric fields influence cell movement by altering membrane dynamics and triggering intracellular signaling mechanisms.

Molecular Pathways in Directional Migration

• Involvement of Small GTPases:

  • GTPases like Rac, Rho, and Cdc42 play crucial roles in coordinating actin dynamics and cell motility across various stimuli.

• Signal Transduction:

  • Different signals initiate similar intracellular pathways, leading to coordinated cell movement.

Conclusion

• Directional migration integrates multiple signals (chemical, mechanical, electrical), using a shared mechanism primarily involving small GTPases and cytoskeletal alterations.

• Understanding these processes can lead to insights in developmental biology and disease contexts, particularly tumor metastasis and tissue regeneration.