Budding and Fission of Nanovesicles Induced by Membrane Adsorption of Small Solutes.

Membrane budding and fission are essential cellular processes that produce new membrane compartments during cell and organelle division, for intracellular vesicle trafficking as well as during endo- and exocytosis. Such morphological transformations have also been observed for giant lipid vesicles with a size of many micrometers. Here, we report budding and fission processes of lipid nanovesicles with a size below 50 nm. We use coarse-grained molecular dynamics simulations, by which we can visualize the morphological transformations of individual vesicles. The budding and fission processes are induced by low concentrations of small solutes that absorb onto the outer leaflets of the vesicle membranes. In addition to the solute concentration, we identify the solvent conditions as a second key parameter for these processes. For solvent conditions, the budding of a nanovesicle can be controlled by reducing the vesicle volume for constant solute concentration or by increasing the solute concentration for constant vesicle volume. After the budding process is completed, the budded vesicle consists of two membrane subcompartments which are connected by a closed membrane neck. The budding process is reversible as we demonstrate explicitly by reopening the closed neck. For solvent conditions, on the other hand, we observe two unexpected morphological transformations of nanovesicles. Close to the binodal line, at which the aqueous solution undergoes phase separation, the vesicle exhibits recurrent shape changes with closed and open membrane necks, reminiscent of flickering fusion pores (kiss-and-run) as observed for synaptic vesicles. As we approach the binodal line even closer, the recurrent shape changes are truncated by the fission of the membrane neck which leads to the division of the nanovesicle into two daughter vesicles. In this way, our simulations reveal a nanoscale mechanism for the budding and fission of nanovesicles, a mechanism that arises from the interplay between membrane elasticity and solute-mediated membrane adhesion.