On protein crowding and bilayer bulging in spontaneous vesicle formation

Spontaneous aggregation of lipids into bilayers and vesicles is a key property for the formation of biological membranes. Understanding the compartmentalization achieved by vesicle formation is an important step toward understanding the origin of life, and is crucial in current efforts to develop artificial life. Spontaneously formed vesicles may be applied as artificial cells if they can efficiently encapsulate biomacromolecules. Recent studies report an enhanced concentration of encapsulated proteins during vesicle formation. In order to obtain more insight into this encapsulation process, here we simulate the spontaneous transition of flat bilayers to vesicles in the presence of solvated model proteins using molecular dynamics simulations. In the bilayer-vesicle transition, which is found to be unaffected by the presence of the solvated proteins, the bilayer edge remains at almost the same height, while the center of the membrane bulges out, a molecular pathway we denominate "bilayer bulging". This bulging results in an interior protein concentration that is significantly lower than that of the solution. By means of an increased protein-membrane interaction, enhanced encapsulation of proteins inside the vesicles could be achieved in our simulations.