Abstract
Of the many biophysical techniques now being brought to bear on studies of membranes, electron paramagnetic resonance (EPR) of nitroxide spin probes was the first to provide information about both mobility and ordering in lipid membranes. Here, we report the first prediction of variable temperature EPR spectra of model lipid bilayers in the presence and absence of cholesterol from the results of large scale fully atomistic molecular dynamics (MD) simulations. Three types of structurally different spin probes were employed in order to study different parts of the bilayer. Our results demonstrate very good agreement with experiment and thus confirm the accuracy of the latest lipid force fields. The atomic resolution of the simulations allows the interpretation of the molecular motions and interactions in terms of their impact on the sensitive EPR line shapes. Direct versus indirect effects of cholesterol on the dynamics of spin probes are analysed. Given the complexity of structural organisation in lipid bilayers, the advantage of using a combined MD‐EPR simulation approach is two‐fold. Firstly, prediction of EPR line shapes directly from MD trajectories of actual phospholipid structures allows unambiguous interpretation of EPR spectra of biological membranes in terms of complex motions. Secondly, such an approach provides an ultimate test bed for the up‐to‐date MD simulation models employed in the studies of biological membranes, an area that currently attracts great attention.
Highlights
Phospholipid bilayers have been extensively investigated and employed as models of biological membranes over the past decades [1]
The presence of CHOL induces an ordering of the acyl chains of DPPC and other saturated lipids leading to the formation of a liquid ordered (Lo) phase
This study reports the first prediction of the Variable Temperature (VT) Electron Paramagnetic Resonance (EPR) spectra of lipid bilayers in the absence and presence of CHOL doped with structurally different spin probes directly and completely from state-of-the-art Molecular Dynamics (MD) simulations
Summary
Phospholipid bilayers have been extensively investigated and employed as models of biological membranes over the past decades [1]. Similar to the case of pure DPPC doped with 5-PC, the temperature variation of predicted outer peak positions in EPR spectra obtained from the MD trajectories for the DPPC:CHOL mixture is in very good agreement with experimental measurements confirming the accuracy of MD simulation model employed in this study.
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