Self-assembly of cholesterol-modified nucleosides into microtubes: Characterization, functionalization, loading and release of model substances

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We have recently discovered that mixtures of phospholipid and a cholesteryl-nucleoside conjugate self-assemble into nano- and microtubes in aqueous solutions. The diameter of these tubes can be controlled depending upon preparation conditions. The goal of this project is to understand this selfassembly process and to utilize these structures as versatile reservoirs for drugs and mediator molecules. To this end, we will study the physico-chemical properties of these nucleolipid-based tubes, aiming to elucidate their mechanism of formation and the role of the multiple parameters that control the self-assembly. The rational design of new nucleolipid conjugates will allow us to probe the specific contributions of the different functional groups as well as to analyze the intermolecular interactions that determine the structure of the tubes. Using a combination of biophysical methods, we will study the composition, morphology, and stability of the tubes under varying experimental conditions. This approach will provide the necessary insight to develop a “tunable” system that can be tailored to display characteristic properties. As a first step in this line, we will test the capability of the nucleolipid tubes to act as reservoirs for model molecules, studying their entrapment and release. In addition, we will explore strategies for the surface functionalization of the tubes with lipophilic molecules. Finally, we will evaluate their biocompatibility in model cell culture systems.