Polysaccharide functionalization reduces lipid vesicle stiffness and increases their performance for MRNA delivery to cells

The biophysical properties of lipid vesicles are important for their stability and integrity; they are also important for controlling the performance when these vesicles are used for drug delivery. The vesicle properties are determined by the composition of lipids used to form the vesicle. However, for a given lipid composition, they can also be tailored by tethering of polymers to the membrane. Typically, synthetic polymers like polyethylene glycol are used to increase vesicle stability but polysaccharides are much less explored. Here, we report a general method to functionalize lipid vesicles with polysaccharides by binding them to cholesterol. We incorporate the polysaccharides on the outer membrane leaflet of giant unilamellar vesicles (GUVs) and investigate their effect on membrane mechanics using micropipette aspiration. We find that the presence of the glycolipid produces an unexpected softening of GUVs with fluid-like membranes. By contrast, the functionalization of GUVs with polyethylene glycol does not reduce their stretching modulus. Furthermore, we explore the effect of polysaccharide functionalization of lipid vesicles for drug delivery. We find that it increases the uptake of small unilamellar vesicles (SUVs) by cells and leads to an improved transfection.This work provides the potential means to study membrane-bound meshworks of polysaccharides similar to the cellular glycocalyx; moreover, it can be used for tuning the biophysical properties of drug delivery vehicles.