Abstract
Nanovesicles are closed, bubblelike surfaces with a diameter between 20 and 200 nm, formed by lipid bilayers and biomembranes. Electron microscopy (EM) studies have shown that these vesicles can attain both spherical and nonspherical shapes. One disadvantage of EM methods is that they provide only a single snapshot of each vesicle. Here, we use molecular dynamics simulations to monitor the morphological transformations of individual nanovesicles. We start with the assembly of spherical vesicles that enclose a certain volume of water and contain a certain total number of lipids. When we reduce their volume, the spherical vesicles are observed to transform into a multitude of nonspherical shapes such as oblates and stomatocytes as well as prolates and dumbbells. This surprising polymorphism can be controlled by redistributing a small fraction of lipids between the inner and outer leaflets of the bilayer membranes. As a consequence, the inner and the outer leaflets experience different mechanical tensions. Small changes in the vesicle volume reduce the overall bilayer tension by 2 orders of magnitude, thereby producing tensionless bilayers. In addition, we show how to determine, for a certain total number of lipids, the unique spherical vesicle for which both leaflet tensions vanish individually. We also compute the local spontaneous curvature of the spherical membranes by identifying the first moment of the spherically symmetric stress profiles across the lipid bilayers with the nanoscopic torque as derived from curvature elasticity. Our study can be extended to other types of lipid membranes and sheds new light on cellular nanovesicles such as exosomes, which are increasingly used as biomarkers and drug delivery systems.
Highlights
Nanovesicles are closed, bubblelike surfaces with a diameter between 20 and 200 nm, formed by lipid bilayers and biomembranes
Even smaller nanovesicles are frequently observed such as synaptic vesicles with a diameter that varies between 20 and 50 nm[4,5] as well as exosomes, which represent small extracellular vesicles with a diameter between 25 and 100 nm.[6−8] In recent years, exosomes and somewhat larger extracellular vesicles have been intensely studied as possible biomarkers for diseases and as targeted drug delivery systems.[9−12]
We directly demonstrate that molecular simulations provide a powerful method to explore the polymorphism of nanovesicles in a systematic manner by adjusting only three control parameters: the vesicle volume, the total number Nlip of lipids assembled in the bilayer, as well as the lipid number Nol or Nil = Nlip − Nol within one of the two leaflets
Summary
Thereby constructing the inner and outer leaflets, respectively. The assembled vesicles enclosed a certain number Nwisp of water beads which defined the initial vesicle volume. We studied spherical vesicles which contained the same total number of lipids, Nlip, but slightly different lipid numbers Nol and Nil = Nlip − Nol within the inner and outer bilayer leaflets Four such vesicles are displayed in the leftmost column of Figure 1a−d, corresponding to volume parameter v. We first assembled spherical vesicles by placing lipid molecules onto two spherical shells corresponding to the two leaflets of the bilayer membranes The size of these vesicles was primarily determined by the vesicle volume, i.e., by the number of water beads enclosed by the inner leaflet of the membrane. The two leaflets of the bilayers contain somewhat different lipid numbers, Nol and Nil, within their outer and inner leaflets
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