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Anja Stulz

Anja Stulz

Interaction of drugs and biomolecules with lipid membranes

Principal investigator: Prof. Dr. Heiko Heerklotz

Institute of Pharmaceutical Sciences
Pharmaceutical Technology and Biopharmacy
Hermann-Herder-Str. 9
79104 Freiburg

Phone: +49 (0) 761-203-4902
anja.stulz@pharmazie.uni-freiburg.de

Abstract

The lipid matrix is the principal barrier for transmembrane transport of drugs, biomolecules, and other active agents, and the medium for their diffusion to their targets within the membrane. Nevertheless, the effects of lipids are often neglected when drug effects are studied. Biophysical interaction studies with model membranes can help us to understand the mechanism of action of membrane-active agents and the critical role of lipids in the transport of drugs and other biomolecules. Better understanding of mechanisms by which drugs may cross or bind to biological membranes could play an important role in developing new drug molecules or efficient drug delivery systems.

One specific objective is the elucidation of membrane-permeabilizing effects of antimicrobial polymers (synthetic mimics of antimicrobial peptides, SMAMPs) which offer a promising alternative to classical antibiotics. Common to antimicrobial peptides and polymers is the ability to cluster lipids through lipid selection and recruitment from a mixed membrane. The positively charged polymers efficiently cluster negatively charged lipids via electrostatic interactions and induce leakage in lipid vesicles by transient defects. We aim to understand the role of the lipid composition in lipid clustering. Systematic variation of the host lipid will reveal which discrepancy between clustered and matrix lipid is responsible for vesicle leakage.


Methods

Artificial membrane systems (liposomes, monolayer), Microcalorimetry,Time-resolved fluorescence spectroscopy, Dynamic light scattering, Zeta potential measurements, Asymmetric Flow-Field-Flow-Fractionation