Cholesterol is an essential component of mammalian cells and its distribution in the organism is
facilitated by so-called lipoprotein particles. Excess cholesterol from the cells is transferred to high-
density lipoproteins (HDLs) and then disposed of by the liver with the bile. An imbalance in the
cholesterol level caused by food intake or genetic factors leads to its accumulation on the arterial wall;
this leads to cell membrane stiffening and influences vascular integrity, signal transduction and
absorption and transport processes and finally to arteriosclerosis, one of the most common causes of
death in industrialized countries.
The challenge is still to understand the function of lipoproteins on a molecular level in order to describe
physiological processes and thus be able to treat disorders such as hypercholesterolemia, heart disease,
stroke and neurodegenerative diseases. In addition, the production and/or targeted manipulation of
lipoproteins offers new possibilities for the transport of therapeutic agents, as lipoproteins can be
remodeled.
Our hypothesis is that, on the one hand, the physical properties of the cellular membrane and, on the
other hand, the specific structure of lipoproteins can strongly influence the transfer of cholesterol and
thus impair the removal of excess lipids from the bloodstream. New knowledge about the uptake
mechanism will clarify how cargo molecules like cholesterol are transferred from the outer envelope of
lipoproteins to cells.
Therefore, in the present project the relationship between receptor-mediated and direct lipoprotein
interaction and the subsequent transfer process with model membranes and finally living cells will be
analyzed and quantified. Using a broad spectrum of complementary and sophisticated measurement
techniques such as combined single-molecule fluorescence and atomic force microscopy, high-speed
scanning force microscopy and fluorescence cross-correlation spectroscopy, it will be possible to gain
a more detailed insight into the underlying biomolecular mechanisms.