GLYCHOL · Glycolipid cholesterol interactions: towards an understanding of mechanisms of lipid raft formation
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2005-11-01 → 2007-10-31
- EU contribution
- €165,792
- Participants
- 1
- Scheme
- EIF
Lines connect the coordinator with its partners.
Results in brief
Final Activity Report Summary - GLYCHOL (Glycolipid Cholesterol interactions: Towards an understanding of mechanisms of lipid raft formation)
The main goal of this project was to elucidate atom level interactions between lipids involved in formations of microdomains called rafts present in cellular membranes. Rafts are composed mainly of sphingolipids, glycolipids and cholesterol and are involved in numerous cellular functions. In order to do this in series of molecular dynamics simulations of rafts components were performed. According to the schedule of the project simulations of systems composed of: 1) simple glycerol based glycolipids, 2) sphingosine based glycolipids 3) glycolipids with cholesterol, and 4) cholesterol and other sterol were performed. These simulations also included numerous methodological tests. Deviation from the original schedule was minor, mainly due to more extensive studies of the 4 points listed above. The results of this work were published in 14 publications in key journals like Physical Review Letters, Biophysical Journal and Journal of Physical Chemistry B, 5 manuscripts are submitted and 2 more will be prepared. Results obtained during the course of this project are highly relevant to both basic and applied sciences. They describe basic interactions in lipid bilayers and provide the first unique data about the specificity of glycolipids and the interaction of glycolipids with cholesterol. The part of the research concerning the cholesterol precursors is of medical importance. It should be stressed that this research attracted the direct interest of the pharmacological industry.
Data: CORDIS, © European Union
Project objective
Lipid rafts have been proposed to play a major role in protein functionality in cellular membranes, yet the underlying physical mechanisms are not properly understood. Here, we propose a project focusing on atomistic level understanding of a number of fundamentally important issues related to raft formation. We employ atomistic molecular dynamics simulations to a variety of bi-layer systems that have been suggested to play a key role in lipid rafts. Specifically, we aim to resolve structural as well as dynamical differences between glycolipid-cholesterol, phosphatidylcholine-cholesterol and sphingomyelin-cholesterol membrane systems.Hydrogen bond networks between lipid head-groups, hydration, water -mediated interactions of head-groups, and van der Waals intera ctions between hydrocarbon chains are of special interest. Correlation between these interactions and the bilayer structure and dynamics will be elucidated. Overall, results obtained in this project allow us to better understand the atomic level mechanisms of raft formation and, consequently, protein function.
Original text from CORDIS.
Participants
- HELSINKI UNIVERSITY OF TECHNOLOGY · ESPOOCoordinatorFinland
Links
Data: CORDIS, © European Union