Formins and Arp2/3 Reciprocally Regulate Contact Guidance on Aligned Collagen Fibrils

Area of Science:

• Cell Biology
• Biomaterials Science
• Mechanobiology

Background:

• Directed cell migration, crucial for biological processes, is influenced by the extracellular matrix (ECM) through contact guidance.
• The precise mechanisms by which cells sense and respond to aligned ECM fibrils, and the roles of internal regulators like formins and Arp2/3, remain unclear.

Purpose of the Study:

• To investigate how cells respond to aligned collagen fibrils and the roles of cytoskeletal regulators in contact guidance.
• To elucidate the contributions of myosin contractility, formins, and Arp2/3 to cell migration on aligned ECM.

Main Methods:

• Development of a novel system to assemble aligned collagen fibrils on mica and transfer them to controllable substrates.
• Utilizing this system to probe contact guidance responses in various cell types.

Main Results:

• Cellular contractility, specifically through myosin, is the primary driver of contact guidance, not receptor expression.
• Highly contractile cells exhibit strong contact guidance, while weakly contractile cells show minimal response.
• Formins promote contact guidance by mediating linear F-actin, whereas Arp2/3 inhibits it by forming branched F-actin structures.

Conclusions:

• Myosin-mediated contractility is essential for effective contact guidance.
• Formins and Arp2/3 act antagonistically to regulate contact guidance, offering potential targets for therapeutic intervention.
• This study provides a new materials system for studying cell-matrix interactions and contact guidance.