assymcurv · The influence of the cell membrane asymmetry and curvature on the functioning of membrane proteins and the transport of therapeutic compounds

The influence of the cell membrane asymmetry and curvature on the functioning of membrane proteins and the transport of therapeutic compounds

Real cell membranes are essentially asymmetric and non-planar. Outer leaflets of the plasma membranes contain neutral lipids and glycolipids, while the inner leaflets host practically all anionic lipids and phosphoinositides. In addition to asymmetric composition the membranes are usually curved due to spontaneous curvature of the membrane lipids and an influence of membrane proteins and cytoskeleton. There are many cellular phenomena, which are influenced by the asymmetry and the membrane curvature. In this work we propose comprehensive interdisciplinary study of the influence of membrane asymmetry and curvature on the functioning of integral membrane proteins (such as lactose permease and photosynthetic reaction centers) and the transmembrane transport of therapeutic compounds (such as cisplatin and its derivatives, squalene-based drugs, etc). The goal is to reveal major physical factors, which distinguish asymmetric and curved membrane environment, govern interactions in the membranes and determine orientation and diffusion of the small molecules (drugs) and large integral membrane proteins. The combination of experimental methods and computer simulations would be used in the project in complimentary manner. The objectives of the project are the following: 1) To develop convergent methodology of studying curved and asymmetric lipid membranes by the combination of experimental techniques and computer simulations. 2) To study the influence of the membrane asymmetry and curvature on the translocation of anti-cancer drugs through the membranes. 3) To determine molecular determinants of the drug molecules, which maximize their cellular uptake and translocation through the membrane depending on the membrane lipid composition and curvature. 4) To study the influence of the membrane lipid charge asymmetry and curvature on integral membrane proteins. 5) To investigate the influence of the membrane environment on behavior of anti-cancer drugs and drug delivery systems based on nanoparticles.

Data: CORDIS, © European Union