Self-assembly of cholesterol-modified nucleosides into microtubes: characterization, functionalization, loading and release of model substance
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 self-assembly 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 analyse 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.
Financer
Duration of project
Start date: 06/2011
End date: 09/2015
Publications
Losensky, L., Goldenbogen, B., Holland, G., Laue, M., Petran, A., Liebscher, J. Scheidt, H. A., Vogel, A., Huster, D., Klipp, E., and Arbuzova, A. Micro- and nano-tubules built from loosely and tightly rolled up thin sheets. Phys. Chem. Chem. Phys., 2016, 18, 1292-1301.
Losensky, L., Chiantia, S., Holland, G., Laue, M., Petran, A., Liebscher, J. and Arbuzova, A. Self-assembly of a
cholesteryl-modified nucleoside into tubular structures from giant unilamellar vesicles. RSC Adv., 2015, 5,
4502–4510.
Serien, D., Grimm, C., Liebscher, J., Herrmann, A., and Arbuzova A. DNA-controlled aggregation of virus like
particles – mimicking a tetherin-like mechanism. New J. Chem., 2014, 38, 5181–5185.
Schade, M., Berti, D., Huster, D., Herrmann, A., and Arbuzova A. Lipophilic nucleic acids – a flexible construction
kit for organization and functionalization of surfaces. Adv. Colloid Interface Sci., 2014, 208, 235–251.
Schade, M., Knoll, A., Vogel, A., Seitz, O., Liebscher, J., Huster, D., Herrmann, A., and Arbuzova, A. Remote
control of lipophilic nucleic acids domain partitioning by DNA hybridization and enzymatic cleavage. J. Am.
Chem. Soc., 2012, 134, 20490–20497.
P. Pescador, N. Brodersen, H.A. Scheidt, M. Loew, G. Holland, N. Bannert, J. Liebscher, A. Herrmann, D. Huster, and A. Arbuzova. Microtubes self-assembled from a cholesterolmodified nucleoside. Chem. Commun., 2010, 46:5358-5360.
