Traction-regulated persistence governs durotaxis across cell types

Area of Science:

• Cellular mechanics and biophysics
• Cancer biology and metastasis
• Biomaterials science and tissue engineering

Background:

• Cell migration along stiffness gradients (durotaxis) is crucial for development and cancer metastasis.
• The precise mechanisms governing durotaxis and its universality across cell types remain incompletely understood.

Purpose of the Study:

• To investigate the roles of cellular traction forces and directional persistence in dictating cell migration along stiffness gradients.
• To elucidate a unified mechanism for durotaxis bias across different cell types and migration behaviors.

Main Methods:

• Utilized tunable poly(ethylene glycol) (PEG) hydrogels with defined stiffness gradients (1-16 kPa).
• Perturbed cellular contractility (using blebbistatin, oligomycin) and adhesion (using vinculin mutants) in cancer cells.
• Developed and validated a computational model integrating traction forces and F-actin stability to predict durotaxis.

Main Results:

• Cells with high traction forces exhibited persistent migration towards stiffer environments (positive durotaxis).
• Cells with reduced traction forces lost persistence and migrated towards softer environments (negative durotaxis).
• Computational model successfully linked stiffness-dependent traction to persistence, capturing both durotaxis behaviors with a single parameter set.

Conclusions:

• Established a unified mechanism where traction-regulated persistence governs durotaxis bias, applicable across cell types.
• Demonstrated that modulating myosin activity or adhesion reinforcement can switch durotaxis states.
• Findings provide insights for designing biomaterials for directed cell migration and developing therapeutic strategies for tissue repair and cancer.