Pseudopeptosomes: non-lipidated vesicular assemblies from bispidine-appended pseudopeptides

We report a novel molecular topology-based approach for creating reproducible vesicular assemblies in different solvent environments (including aqueous) using specifically designed pseudopeptides. Deviating from the classical "polar head group and hydrophobic tail" model of amphiphiles, we showed (reversible) self-assembly of synthesized pseudopeptides into vesicles. Naming these new type/class of vesicles "pseudopetosomes", we characterized them by high-resolution microscopy (scanning electron, transmission electron, atomic force, epifluorescence and confocal) along with dynamic light scattering. While accounting for hydropathy index of the constituent amino acids (side chains) of pseudopeptides, we probed molecular interactions, resulting in assembly of pseudopeptosomes by spectroscopy (fourier-transform infrared and fluorescence). Molecular characterization by X-ray crystallography and circular dichroism revealed "tryptophan (Trp)-Zip" arrangements and/or hydrogen-bonded one-dimensional assembly depending on specific pseudopeptides and solvent environments. Our data indicated that pseudopeptosomes are formed in solutions by self-assembly of bispidine pseudopeptides (of Trp, leucine and alanine amino-acid constituents) into sheets that transform into vesicular structures. Thus, we showed that assembly of pseudopeptosomes utilizes the full spectrum of all four weak interactions essential in biological systems. Our findings have direct implications in chemical and synthetic biology, but may also provide a new avenue of investigations on origins of life via pseudopeptosome-like assemblies. We also showed that these designer peptides can act as carriers for cellular transport.