Aggregation and vesiculation of membrane proteins by curvature-mediated interactions

Abstract

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.

Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects

“…[43][44][45][46][47] The occurrence of the interaction depends on whether the amount of energy released from the binding of the MSNs with the RBC membrane (E i ) is able to overcome the amount of free energy required to bend the membrane and adapt to the surface of MSNs (E b ). The former energy is associated with the external surface area (i.e., accessible silanols) of MSN, 30 while the latter is proportional to the curvature or inversely proportional to the square of the radius (r) of the particle.…”

Multiscale modeling of emergent materials: biological and soft matter

“…However, membrane mediated interactions lead to the attraction of several such local membrane benders, which by driving a large morphology change can then cooperatively create a joint budding vesicle. For instance, the highly bent structure in the middle will detach from the membrane through a fission event within the next 30 ms. 215 developments, especially the recent work of Haataja et al 222 related to lipid rafts.…”

What do diffusion measurements tell us about membrane compartmentalisation? Emergence of the role of interprotein interactions

“…Currently, molecular dynamics simulates natural systems whereby several proteins are embedded in a lipid bilayer [61]. Despite the short time scale of these simulations (a few microseconds), Periole and collaborators [62] have simulated a quasi-all-atom description of rhodopsin in a phosphatidylcholine bilayer containing more than 1,000 lipids and up to 16 proteins.…”

“…This model has been shown to be valid in two dimensions for membrane proteins [55]. Proteins clusters in cell or model membranes can result from a combination of non-specific shortrange attractions and longer-range weaker repulsions (see "Appendix 2" for details) [60].Currently, molecular dynamics simulates natural systems whereby several proteins are embedded in a lipid bilayer [61]. Despite the short time scale of these simulations (a few microseconds), Periole and collaborators [62] have simulated a quasi-all-atom description of rhodopsin in a phosphatidylcholine bilayer containing more than 1,000 lipids and up to 16 proteins.…”