Lysolipids such as monoacyl-glycero-phosphatidylcholines are products of phospholipases and play roles in signaling and as an energy source in biology. They and their analogs (such as miltefosine) are used as drugs, for drug delivery systems and as biological detergents for membrane protein solubilization. On their own, they for micelles and behave in a detergent-like manner but a closer look shows a number of unusual effects regarding their interaction with membranes. Lysolipids added to fluid phosphatidylcholine bilayers insert into the cis lipid leaflet but do not flip to the trans side over many hours or days. As a consequence, they induce area asymmetry the first induces the budding of very small, highly lysolipid-enriched exovesicles. This relaxed area asymmetry but is limited in extent since it “uses up” excess area of the membrane and, hence, comes to a halt as “mother vesicles” approach a smooth spherical shape. Additional lysolipid added the system is staying out of the membrane since asymmetry stress costs more energy than insertion would yield. Lysolipid-containing liposomes of dipalmitoylphosphatidylcholine (DPPC) and PEGylated lipid act as thermoresponsive drug delivery systems. The are stable and retain their cargo (e.g., doxorubicin) safely upon storage and at 37°C, when the lipid is in the gel phase. As the liposomes enter hyperthermic regions in the body, they induce a fast yet transient drug release. This had been explained by a detergent-like effect but paradoxically, other detergents induce leakage and membrane destruction upon freezing – not melting. The paradox is resolved by the finding that beyond about 5 mol% in a gel phase, lysolipids demix from the bilayer to form stable, chain-interdigitated domains with a high lysolipid content of >30 mol%. The trigger point (10 mol% lysolipid, 41°C) is a eutectic point where both phases melt at once, creating transient spots with high, membrane-permeabilizing lysolipid content.

15:00: Coffee Break

 15:15: Chetan Poojari (B7, AG Hub): Fusion peptides modulate free-energies of stalk  formation

 15:30: Cynthia Alsayyah (C10, AG Ernst): Modulating membrane compressibility using cyclodextrins to study membrane proteins

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