Membrane inward/outward budding and transition pathway induced by the asymmetric solutions

Abstract

The study of membrane morphology transitions is crucial for understanding various biological processes, such as cell division, and intracellular vesicle transport. In this work, we aim to clarify the molecular mechanism underlying the asymmetric solution-induced membrane shape transition in lipid bilayers. Using giant unilamellar vesicles (GUVs) as model membranes, we investigated the interaction of fully hydrated lipid membranes with two distinct sugar solutions—glucose and sucrose. We applied advanced imaging techniques and theoretical analyses to study membrane deformation and its transition pathways. Our experimental observations revealed that asymmetric sugar solutions induce spontaneous curvature in the phospholipid bilayer, resulting in the formation of outward(/inward) budding vesicles over a wide range of parameters. The direction of the curvature can be reversed by exchanging the internal and external solutions, indicating that the sugar-lipid interactions generate a significant positive(/negative) spontaneous curvature. Theoretically, we attempted to determine the parameter range of stable membrane shapes (i.e., phase diagram) using two dimensionless physical parameters—volume-to-area ratio and normalized spontaneous curvature. Obtaining a phase diagram helps identify the transition pathways of GUVs membrane shapes (experimentally, we captured two possible outward budding vesicles and one inward budding vesicle transition pathway). Our findings can be extended to other types of lipid membranes and provide new insights into the deformation of cell-like micron-sized vesicles, such as exosomes and endosomes, which are increasingly used as biomarkers and drug delivery systems. Moreover, lipid vesicles containing anticancer drugs exhibit fewer side effects than non-liposomal anticancer agents and can effectively target solid tumors.