Reevaluating the membrane organization, phase behaviour, aggregation, and fusion of the model membranes under different external influences

Abstract

It is well known that Alec Bangham discovered and proposed the idea of using liposomes as the drug delivery systems. Since then, liposomes have become an indispensable part of research and clinical applications in the field of nanomedicine, due to the several advantages e. g. loading ability of both hydrophobic and hydrophilic drugs, tunable size and surface charge, biodegradability, and biocompatibility, etc. One of the main advantages is that lipid vesicles can mimic the cellular membranes which can be conveniently designed in vitro using lipids and simplify the in vivo complex membrane environment for easier analysis. Lipid vesicles are prone to fuse which limits their application as a delivery system and several modifications have been introduced to enhance the targeted delivery. Therefore, in order to modify and stabilize their structures, they are often treated with external interactive species e. g. nanoparticles, biomolecules, polymers, etc. On the other hand, membrane fusion is a fundamental process in many important biological processes such as viral infection, endocytosis, and exocytosis, etc. This process both in vivo and in vitro is usually controlled by external agents called fusogens. The most common fusogens are large molecules like proteins and peptides and they play a vital role in different processes of cells such as self reproduction, fusion, and fission which are also crucial steps for mimicking the origin of cellular life. Phospholipid vesicle formation in cells e. g. vesicular transport and organelle biogenesis are critically dependent on membrane fission, which is induced by highly evolved proteins. Therefore, both the stabilization and destabilization of the lipid vesicles have been considered of great interest due to their own perspective. Thus the interactions of lipid vesicles with external species are extremely important to understand the potential changes in the membrane properties. These interactions can influence the hydration-dehydration, rigidity, and fluidity of the lipid bilayer. Even minor changes in the membrane structure and properties can have larger impacts on several important biological functions. Several complex biological processes are associated with the changes in the membrane phase state. For example, the fluid mosaic model suggested by Singer and Nicolson proposed that the fluid state of membrane lipids is critical for membrane function. On the other hand, the initial membrane phase state of the delivery system can be changed to either an ordered or disordered phase state by different external entities which consequently affects the releasing ability of the payload from the delivery system. The determination of the membrane phase state required complex instrumentations. Therefore, it is always important and recommended for quick determination of the membrane phase state using simple techniques. The dynamical properties of the membrane were previously investigated by using organic membrane probes (e. g. PRODAN, LAURDAN, ANS, etc.). However, to study the morphological changes in the lipid vesicles via imaging technique (i. e. for confocal microscopy) we had to use external dyes (e. g. Rhodamine B) or lipid-tagged dyes (modified dyes) due to the multiple disadvantages of these organic membrane probes. In this context, luminescence carbon dots (CDs) have several advantages over the conventional organic membrane probes owing to their tunable photoluminescence, high quantum yield, excellent photostability, and broad excitation-emission spectral range. Therefore, a CD-based membrane probe should be advantageous compare to the organic membrane probe, which possibly discovers a new horizon for the bioimaging models. The membrane interaction studies account for the underlying mechanisms and the resultant influence at the nano-bio interface which eventually affects the cellular processes. Thus, a better understanding of the interactions at the membrane interface is required, which can help us to bridge the gap between the lipid systems in vivo and in vitro.