Aggregation and vesiculation of membrane proteins by curvature-mediated interactions

• Published in: Nature Vol. 447; no. 7143; pp. 461 - 464
• Main Authors: Kremer, Kurt, Deserno, Markus, Reynwar, Benedict J, Illya, Gregoria, Harmandaris, Vagelis A, Müller, Martin M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 24.05.2007; Nature Publishing Group
• Subjects: Attraction; Binding sites; Biological and medical sciences; Capsid - chemistry; Capsid - metabolism; Capsid - ultrastructure; Cell Membrane - chemistry; Cell Membrane - metabolism; Cell Membrane - ultrastructure; Cell physiology; Cellular biology; Colloids - chemistry; Computer Simulation; Curvature; Endoplasmic reticulum; Endoplasmic Reticulum - chemistry; Endoplasmic Reticulum - metabolism; Energy; Fundamental and applied biological sciences. Psychology; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipids - analysis; Lipids - chemistry; Mathematical analysis; Mathematical models; Membrane and intracellular transports; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Membranes; Models, Molecular; Molecular and cellular biology; Nanoparticles - chemistry; Protein Binding; Proteins; Remodeling; Simulation; Theory; Aggregation; Remodelling; Membrane protein; Membrane transport; Curvature; Plasma membrane
• ISSN: 0028-0836; 1476-4687; 1476-4679
• DOI: 10.1038/nature05840

Membrane remodelling plays an important role in cellular tasks such as endocytosis, vesiculation and protein sorting, and in the biogenesis of organelles such as the endoplasmic reticulum or the Golgi apparatus. It is well established that the remodelling process is aided by specialized proteins that can sense as well as create membrane curvature, and trigger tubulation when added to synthetic liposomes. Because the energy needed for such large-scale changes in membrane geometry significantly exceeds the binding energy between individual proteins and between protein and membrane, cooperative action is essential. It has recently been suggested that curvature-mediated attractive interactions could aid cooperation and complement the effects of specific binding events on membrane remodelling. But it is difficult to experimentally isolate curvature-mediated interactions from direct attractions between proteins. Moreover, approximate theories predict repulsion between isotropically curving proteins. Here we use coarse-grained membrane simulations to show that curvature-inducing model proteins adsorbed on lipid bilayer membranes can experience attractive interactions that arise purely as a result of membrane curvature. We find that once a minimal local bending is realized, the effect robustly drives protein cluster formation and subsequent transformation into vesicles with radii that correlate with the local curvature imprint. Owing to its universal nature, curvature-mediated attraction can operate even between proteins lacking any specific interactions, such as newly synthesized and still immature membrane proteins in the endoplasmic reticulum.