Predicting the Size and Properties of Dendrimersomes from the Lamellar Structure of Their Amphiphilic Janus Dendrimers

Abstract

Dendrimersomes are stable, monodisperse unilamellar vesicles self-assembled in water from amphiphilic Janus dendrimers. Their size, stability, and membrane structure are determined by the chemical structure of Janus dendrimer and the method of self-assembly. Comparative analysis of the periodic arrays in bulk and dendrimersomes assembled by ethanol injection in water of 11 libraries containing 108 Janus dendrimers is reported. Analysis in bulk and in water was performed by differential scanning calorimetry, X-ray diffraction, dynamic light scattering, and cryo-TEM. An inverse proportionality between size, stability, mechanical properties of dendrimersomes, and thickness of their membrane was discovered. This dependence was explained by the tendency of alkyl chains forming the hydrophobic part of the dendrimersome to produce the same local packing density regardless of the branching pattern from the hydrophobic part of the dendrimer. For the same hydrophobic alkyl chain length, the largest, toughest, and most stable dendrimersomes are those with the thinnest membrane that results from the interdigitation of the alkyl groups of the Janus dendrimer. A simplified spherical-shell model of the dendrimersome was used to demonstrate the direct correlation between the concentration of Janus dendrimer in water, c, and the size of self-assembled dendrimersome. This concentration-size dependence demonstrates that the mass of the vesicle membrane is proportional with c. A methodology to predict the size of the dendrimersome based on this correlation was developed. This methodology explains the inverse proportionality between the size of dendrimersome and its membrane thickness, and provides a good agreement between the experimental and predicted size of dendrimersome.

Self-assembly of amphiphilic Janus dendrimers into uniform onion-like dendrimersomes with predictable size and number of bilayers

“…As previously reported for single-bilayer dendrimersomes, their size increases with the increase of the concentration of the Janus dendrimer injected in water (27,35). Onion-like vesicles were found to exhibit a similar size-concentration dependence.…”

“…2). "Single-single" amphiphilic Janus dendrimer refers to a compound constructed from a "single" hydrophilic and a "single" hydrophobic dendron (28), rather than from "twin" hydrophilic and "twin" hydrophobic dendrons (26,27). This modular synthetic approach involves coupling of the hydrophilic acids 3b and 5a-e with the hydrophobic amine minidendron (41) 8a, or hydrophobic acid minidendron 3a with the hydrophilic amine 8b.…”

“…Polymersomes (21)(22)(23)(24) assembled from amphiphilic block copolymers exhibit better mechanical properties and permeability, but are not always biocompatible and are polydisperse. Dendrimersomes (25)(26)(27)(28) self-assembled from amphiphilic Janus dendrimers and minidendrimers (26)(27)(28) have also been elaborated to mimic single-bilayer biological membranes. Amphiphilic Janus dendrimers take advantage of multivalency both in their hydrophobic and hydrophilic parts (23, [29][30][31][32].…”

“…Dendrimersomes are assembled by simple injection (33) of a solution of an amphiphilic Janus dendrimer (26) in a water-soluble solvent into water or buffer and produce uniform (34), impermeable, and stable vesicles with excellent mechanical properties. In addition, their size and properties can be predicted by their primary structure (27). Amphiphilic Janus glycodendrimers self-assemble into glycodendrimersomes that mimic the glycan ligands of biological membranes (35).…”

Janus dendrimersomes coassembled from fluorinated, hydrogenated, and hybrid Janus dendrimers as models for cell fusion and fission

“…A third class of synthetic vesicles denoted dendrimersomes (DSs) has been elaborated by the self-assembly of amphiphilic JDs (11). Their simple preparation by injection of THF, ethanol, and other organic solutions of JDs into aqueous media results in monodisperse assemblies of predictable size with bilayer thicknesses of 4.5-6 nm, which are similar to those of biological membranes (11,12). DSs together with their sugar (glycan)-presenting counterparts glycodendrimersomes (13) combine the biological compatibility of liposomes with the robustness of polymersomes, providing improved synthetic vesicles for mimicking biological membranes including by hybrid coassembly with bacterial membranes (14) and for biomedical applications (15).…”