Membranes and lipids diversity

Tampereen teknillinen yliopisto / Tomasz Rog

Biological membranes regulate and govern all processes in cells. They are involved in energy storage, signaling, cell-cell interactions, and in all functions related to membrane proteins which constitute ~50% of proteins in cells. What is more, there are no cells without a membrane, and even the programmed cell death initiates through the destruction of the membrane. Considering the importance of membranes, it is not surprising to realize that biological membranes are composed of ~100-1,000 different lipid species, each having a certain function. This amazing diversity is currently hardly understood. One of its consequences is formations of lipids domain among which rafts attracts lots of attentions. Lipids rafts are formed of cholesterol and saturated phospho- and glycolipids. The aim of this project is to understand biological role of various lipids group especially in the context of their interaction with cholesterol and involvement or its lack int rafts formation and explain relation between these lipids structure and their function. Methods Main methods used in these studies will be molecular dynamics simulation using Gromacs package. Method used in membrane simulations are generally well tested and known by applicant who published more than 50 articles where MD was major tool. The force-field of choice is OPLS all atom force field, so called Berger lipid force-field, and Gromos force-field. These force-field were already tested in research of same type. Specific algorithms used in simulations are Particle-Mesh-Ewald method for exact calculation of electrostatic interactions, relevant barostat and termostat, constrain algorithms (eg LINX). Models of the lipid bilayer considered in these studies will be composed of 128-512 lipids molecule (40 000 - 120 000 atoms) and will be simulated in most cases for 200 ns. Models 1) First set of models will consist of sphingomieline and 3 chemically modified sphingomielines where methyl groups substitute hydrogen in amide and hydroxyl groups. These lipids will be simulate with and without cholesterol thus total number of simulations will be 8. Aim of these simulations is to find out role of hydrogen bonds created by these functional group in lipid-lipid and lipid-sterol interactions. This project is performed in collaboration with experimental group of prof J. P. Slotte from Abo Academia University and is continuation of recently finished project where modified part of lipid was choline group (publication 14). 2) Second set of models will consist of ether lipids which were recently found to be accumulated in cases of obesity in adipose tissue. These lipids are not well studied and its effect on lipid bilayer properties is mostly unknown. In these models we will select up to 10 models of bilayers which will be composed of lipid species found to be increased in pathological cases. This part of the project will be performed in colaboration with Dr Matej Orestic from VTT who provide exact information about lipid composition. 3) Third set of models will consist of phophatidylcholine as a membrane and porphyrine, average size compound used in photo therapy of cancer. Porphyrin will be placed in various places of the system (membrane interior, water phase, interphase between water and membrane). Since one lipid bilayer can accommodate only 4 porphyrine molecule we will simulate 3 systems with different initial structure to obtain good statistic. Number of system will be next multiplied by 2 since we have to consider two protonation state. Aim of this project is to find optimal location of porphyrin in the lipid bilayer. Although porphyrins are well studied experimentally their locations remains unclear. This might results from preferences to interface between water and membrane which usually lead to difficulties in interpretation of experimental results.