Increased pH-sensitivity of protein binding to lipid membranes through the electrostatic-hydrogen bond switch.

The signaling lipid phosphatidic acid (PA) is believed to interact specifically with membrane-bound globular proteins through a combination of electrostatic interactions and hydrogen bond formation known as the electrostatic-hydrogen bond switch. PA, which adjusts its protonation state according to the ambient pH, is able to regulate protein binding under physiological conditions in a pH-dependent manner. We investigate the question to what extent the electrostatic-hydrogen bond switch contributes to the pH-sensitivity of protein binding.

Modeling the release kinetics of poorly water-soluble drug molecules from liposomal nanocarriers.

Liposomes are frequently used as pharmaceutical nanocarriers to deliver poorly water-soluble drugs such as temoporfin, cyclosporine A, amphotericin B, and paclitaxel to their target site. Optimal drug delivery depends on understanding the release kinetics of the drug molecules from the host liposomes during the journey to the target site and at the target site. Transfer of drugs in model systems consisting of donor liposomes and acceptor liposomes is known from experimental work to typically exhibit a first-order kinetics with a simple exponential behavior.

Transfer mechanism of temoporfin between liposomal membranes.

The transfer kinetics of temoporfin, a classic photosensitizer, was analyzed by investigating the influence of total lipid content, temperature, as well as charge, acyl chain length, and saturation of the lipids in donor vesicles using a mini ion exchange column technique. The obtained results are consistent with an apparent first order kinetics in which the transfer proceeds through both liposome collisions and through the aqueous phase. We present a corresponding theoretical model that accounts for the detailed distribution of drug molecules in donor and acceptor liposomes and predicts the transfer rates as a function of drug concentration and number of donor and acceptor liposomes.

Stability of protein-decorated mixed lipid membranes: The interplay of lipid-lipid, lipid-protein, and protein-protein interactions.

Membrane-associated proteins are likely to contribute to the regulation of the phase behavior of mixed lipid membranes. To gain insight into the underlying mechanism, we study a thermodynamic model for the stability of a protein-decorated binary lipid layer. Here, proteins interact preferentially with one lipid species and thus locally sequester that species.

Influence of monolayer-monolayer coupling on the phase behavior of a fluid lipid bilayer.

We suggest a minimal model for the coupling of the lateral phase behavior in an asymmetric lipid membrane across its two monolayers. Our model employs one single order parameter for each monolayer leaflet, namely its composition. Regular solution theory on the mean-field level is used to describe the free energy in each individual leaflet.