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

Abstract

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 good 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 poor 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.

Remodeling of Membrane Shape and Topology by Curvature Elasticity and Membrane Tension

“…These shape transformations of nanovesicles are, however, accessible to molecular dynamics simulations. [ 16,17,41–45 ] Here, we focus on two recent simulations [ 16,17 ] which revealed that the leaflet tensions and the concentrations of small solutes, which adsorb onto the membranes, represent important control parameters for the nanovesicle morphologies, see Figure 7 and Section 7.3 further below. In particular, these studies identified parameter values for the formation of membrane necks.…”

“…Closed membrane necks viewed on nano and micron scales: a,b) Two examples for the hourglass‐like shape of closed necks on the nanoscale where we still resolve the molecular bilayer. Both exterior solutions contain small solutes such as simple sugars (orange) [ 17 ] : a large solute concentration for good solvent conditions in (a) and a small concentrations for poor solvent conditions in (b); and c,d) Optical images of giant vesicles. The scale bar is 10 µm in (c) and 5 µm in (d).…”

“…Reproduced under terms of the CC‐BY license. [ 17 ] Copyright 2021, The Authors, published by American Chemical Society.…”

“…Using molecular simulations, we recently observed the budding and fission of nanovesicles, induced by the adsorption of small solutes onto the vesicle membranes. [ 17 ] Low concentrations of these solutes were present in the exterior aqueous solution and formed an adsorption layer on the outer leaflet of the vesicle membrane. This adsorption layer generated a significant spontaneous curvature that could be used to change the morphology of the vesicles.…”

“…These shape transformations of nanovesicles are, however, accessible to molecular dynamics simulations as has been recently demonstrated. [ 16,17 ]…”