Dr. Andreas Zumbühl "Mechanosensitive Phospholipid Vesicles - Balance of Forces at Play"

The modular structure of phospholipids allows for a large variety of biophysical properties. Here, we present a combined effort of organic synthesis and biophysics. Our goal is to alter specific parts of the phospholipid structure and study the effects such changes have on phospholipid mono- and bilayer organization.

In particular, we summarize our work on mechanosensitive liposomes. These vesicles are tight in the resting state but release their cargo when submitted to elevated shear stresses. Such high wall-shear stresses are found e.g. when blood is passed from open blood vessels into stenosed blood vessels. The purely physics-based targeting using mechanosensitive liposomes therefore represents a fresh approach in drug delivery.

A set of artificial bis-amido- and bis-urea-phospholipids have been synthesized. Their monolayer and bilayer properties have been analyzed and the dominance of the phospholipid geometry (1,3- vs. 1,2-fatty acid substitution pattern) over the intermolecular hydrogen bonding forces have been noted. The bilayer vesicles form a type II membrane which is discontinuous. The membrane defects are attenuated during vesicle exposure to shear forces, making the liposomes shear sensitive.