Detection and Mechanical Characterization of Small Multilamellar Vesicles using Atomic Force Microscopy

Multilamellar vesicles (MLVs) have beneficial properties over currently used unilamellar vesicles (LUVs) for drug delivery, such as more hydrophobic volume for hydrophobic drugs. Moreover, they may have altered mechanical properties, which are suggested to influence cellular uptake. We investigated the mechanics of small MLVs using atomic force microscopy (AFM). We quantified the mechanical response of single liposomes by AFM nano-indentation. Analyzing the total distance of breaks in force-indentation curves we were able to determine the degree of lamellarity (1-5) of individual vesicles. This allowed us to characterize the influence of multilamellarity on morphological and mechanical properties. We found that MLVs, upon adhesion with a surface, stay in a more spherical shape respect to ULVs. Furthermore, the stiffness increases linearly with the addition of each lipid bilayer (0.0027 N/m added stiffness). We speculate that the added osmotic pressure, due to the inner and less-deformed vesicles, together with their bending, cause the observed stiffening. These results suggest that small MLVs might have beneficial properties for cellular uptake.