Bauer Martin, Membrane Functionalization Using Polyrotaxanes with Modified Cyclodextrins (2011)

This work is aimed at the design and characterisation of a new family of tethered ligands, called sliding tethered ligands (STLs). They are based on topological complexes between polymers and amphiphilic cyclodextrins (CDs), which can be inserted into phospholipid membranes. At first we investigate the membrane insertion properties of amphiphilic cholesteryl CD derivatives, which are suitable membrane anchors for the STLs. With the help of neutron reflectivity it can be demonstrated that the CD residues show a remarkable conformational adaptability and that the CD cavities remain accessible upon insertion into lipid model membranes. We have developed a synthetic pathway to assemble the STLs from polyrotaxanes with a controlled low number of mono-modified azido-α-CDs, threaded on a polyethylene glycol (PEG) chain. Using newly developed in-situ capping methods the polyrotaxanes are endcapped with adamantane ligands, which can be recognized by a β-CD receptor. Furthermore a cholesteryl anchor is attached to the threaded CDs in order to enable the STLs to insert into membranes. We demonstrate that STLs readily insert into phospholipid (DPPC) model membranes using IR Absorption Reflection Spectroscopy and investigating the film morphology by Brewster Angle Microscopy and Atomic Force Microscopy. Applying neutron reflectivity it is shown, that for sufficiently high polymer densities the STLs form polymer brushes, which follow the scaling laws predicted by the mean field theory. Using the surface force apparatus it is evidenced that model membranes modified with STLs and cholesteryl β-CD receptors give rise to typical tethered ligand-receptor interaction profiles.

PhD Manuscript avalaible here