Membrane-mediated interaction between strongly anisotropic protein scaffolds.

Area of Science:

• Biophysics
• Cell Biology
• Computational Biology

Background:

• Intracellular organelle shaping relies on specialized scaffold proteins that induce membrane curvature.
• Effective membrane shaping necessitates protein segregation into domains, driven by protein-protein interactions.
• Previous models of protein-mediated membrane interactions often used simplified assumptions of protein shape and distance.

Purpose of the Study:

• To computationally investigate membrane-mediated interactions between scaffold proteins with highly anisotropic (non-spherical) shapes.
• To quantitatively analyze these interactions for BAR domain proteins, critical for endocytosis.
• To explore the role of scaffold orientation entropy in protein-protein interactions.

Main Methods:

• Computational modeling of membrane-mediated interactions between anisotropic protein scaffolds.
• Inclusion of repulsive forces from scaffold orientation entropy alongside attractive forces from membrane undulations.
• Quantitative analysis of interaction energy for realistic BAR domain geometries.

Main Results:

• Anisotropic scaffold shapes induce mutual alignment and strong attractive forces, leading to close proximity.
• The repulsive force from scaffold orientation entropy is comparable in magnitude to attractive forces from membrane undulations.
• Calculated interaction energy between realistic scaffolds is tens of kBT, ensuring robust domain segregation.

Conclusions:

• Scaffold shape anisotropy is a key factor driving the self-assembly and domain segregation of membrane-shaping proteins.
• These findings provide a quantitative understanding of BAR domain interactions crucial for membrane remodeling in cellular processes like endocytosis.
• The study highlights the importance of considering realistic, anisotropic protein geometries in models of membrane-protein interactions.