Spherical Nanovesicles Transform Into A Multitude Of Nonspherical Shape

Nanovesicles are formed by lipid bilayers and biomembranes with a typical diameter between 20 to 200 nm, frequently used for delivery and/or targeting of drugs, biomolecules and contrast agents. Lipid nanovesicles have also shown great potential in disease diagnosis and cancer biology. Electron microscopic (EM) studies reveal that these vesicles attain both spherical and nonspherical shapes. However EM studies are limited to a single image and cannot reveal the entire pathway of shape transformation of an individual vesicle. Here, we use molecular dynamics simulation to explore the sequential pathway of morphological transformations of nanovesicles. We assemble a series of spherical vesicles which transform into a multitude of nonspherical shapes (prolates, oblates, stomatocytes, dumbbells etc) when we reduce their volume. We find that this surprising polymorphism can be controlled by reshuffling only a few lipids between the inner and outer leaflets of the nanovesicle, keeping the total number of lipids fixed. Such small changes in the lipid distributions generate different mechanical tensions within the individual leaflets. In each case, by slightly tuning the water volume we obtain tensionless bilayers. In fact, we find one unique reference state of the spherical vesicle, for which each bilayer leaflet becomes tensionless individually. We estimate the local spontaneous curvature of these spherical membranes by identifying the microscopic torque as obtained from the stress profiles across the lipid bilayers along with the nanoscopic torque as obtained from curvature elasticity. We further extend our study to the shape transformation of nanovesicles in solution of small solute molecules that adsorb on the membranes of the nanovesicles.