Supramolecular assembly of molecules is the next step in organization from nano- to macroscale, and is therefore a key process in the development of advanced materials (Lehn, 2002). Lipid membrane-based structures also offer a large potential for technological applications in a variety of fields from electronics to biomedicine. Self-assembly of amphiphilic molecules is of fundamental interest with regard to self-organization processes. Covalent coupling of two biological moieties with different properties as a lipid (hydrophobic) and nucleoside or nucleotide (hydrophilic, specific base-pairing, hydrogen-bonding and p-p stacking) allows a new level in controlling the assembly and modification of surfaces.
 i) We have recently assembled multiple layers of intact lipid vesicles on a solid support provided by Layer-by-Layer (LbL) particles using sequence specific Watson-Crick base pairing properties of oligonucleotides and incorporation of lipophilic anchors into membranes (Fig. 1 and (Loew et al., Small 2009). Our approach demonstrates the controlled and reversible building of organized miniature layers of liposomes on small particles that can be manipulated on demand, e.g. using optical tweezers. These particles can be used for controlled release and as nanoreactor.

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ii) We have also recently found that cholesteryl-nucleoside conjugate and natural phospholipids self-assemble into stable microtubules (Fig. 2 and (Pescador et al., Chem. Commun. 2010). The objective of this project proposal is to establish the physico-chemical properties of the novel microtubules and whether these structures could be used to achieve sustained release. We are going to elucidate: 1) what morphology do the microtubules have? 2) What mechanisms are responsible for the tubes formation and how different incubation parameters influence the formation? 3) Can the tubes be used for sustained delivery of drugs and nutrients?

 iii) We are interested in the lateral partitioning of the lipid-modified DNA and peptide nucleic acid (PNA) as specific and controllable regulation of the location at the membrane surface is not only important in cell signaling, motility, and endocytosis, but also would allow diverse biotechnological applications due to the control of interactions on the molecular level (Fig. 3). We have found that tocopherol-modified oligonucleotides partition exclusively into liquid-disordered domains (Kurz et al., Angew. Chem. 2006), whereas cholesterol-modified oligonucleotides partition in both liquid-ordered and liquid-disordered domains (Bunge et al., 2009). Recently we found that palmitoylated PNA partitions almost explicitly into liquid-ordered domains, which allowed us to prepare Janus vesicles with temperature controllable separation and mixing of lipophilic nucleic acids (Loew et al., J. Am. Chem. Soc. 2010).

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iv) Development of targeted and triggerable delivery systems is of high relevance for anti-cancer therapies. We have developed reduction-sensitive liposomes composed of a novel multifunctional lipid-like conjugate – containing disulfide bond and biotin moiety – and natural phospholipids (Goldenbogen et al., Langmuir 2011, Fig. 4). Release of the entrapped cargo from the reduction-sensitive liposomes inside the cells was observed, implying the potential of using our system for active targeting and delivery.