Design principles for robust vesiculation in clathrin-mediated endocytosis

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Cellular trafficking relies on membrane budding, a process sensitive to mechanical forces like membrane tension.
• Clathrin-mediated endocytosis (CME) demonstrates robustness across varying environments, suggesting evolved physical principles.
• Elevated membrane tension can inhibit protein coat-driven membrane budding.

Purpose of the Study:

• To investigate the physical principles governing protein coat-mediated membrane budding under varying mechanical conditions.
• To determine how membrane tension, protein coat properties, and actin polymerization influence bud formation.
• To identify mechanisms ensuring robust vesiculation despite opposing forces.

Main Methods:

• Theoretical modeling of membrane mechanics and protein-coat interactions.
• Systematic investigation of parameters including membrane rigidity, coat curvature, coat area, membrane tension, and actin polymerization force.
• Analysis of bud formation dynamics under different tension regimes.

Main Results:

• At low membrane tension, increased coat area or curvature promotes smooth bud formation.
• High membrane tension flattens the membrane, inhibiting budding.
• Intermediate tensions exhibit a 'snap-through instability,' transitioning from U-shaped to closed buds.
• Increased coat rigidity or actin polymerization force can overcome this instability.
• Combined coat rigidity and actin force ensure robust budding even at high membrane tensions.

Conclusions:

• Protein coat mechanics and external forces play critical roles in regulating membrane budding.
• A 'snap-through instability' at intermediate tensions can be modulated by coat properties and actin forces.
• The interplay between coat rigidity and actin polymerization enables robust cellular vesicle formation under diverse mechanical stresses.