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Updated: Apr 21, 2026

Neutron Spin Echo Spectroscopy as a Unique Probe for Lipid Membrane Dynamics and Membrane-Protein Interactions
Published on: May 27, 2021
NRas slows the rate at which a model lipid bilayer phase separates
Elizabeth Jefferys1, Mark S P Sansom, Philip W Fowler
1Department of Biochemistry, University of Oxford, South Parks Rd, Oxford, OX1 3QU, UK. philip.fowler@bioch.ox.ac.uk.
Abstract:
The Ras family of small membrane-associated GTP-ases are important components in many different cell signalling cascades. They are thought to cluster on the cell membrane through association with cholesterol-rich nanodomains. This process remains poorly understood. Here we test the effect of adding multiple copies of NRas, one of the canonical Ras proteins, to a three-component lipid bilayer that rapidly undergoes spinodal decomposition (i.e. unmixing), thereby creating ordered and disordered phases. Coarse-grained molecular dynamics simulations of a large bilayer containing 6000 lipids, with and without protein, are compared. NRas preferentially localises to the interface between the domains and slows the rate at which the domains grow. We infer that this doubly-lipidated cell signalling protein is reducing the line tension between the ordered and disordered regions. This analysis is facilitated by our use of techniques borrowed from image-processing. The conclusions above are contingent upon several assumptions, including the use of a model lipid with doubly unsaturated tails and the limited structural data available for the C-terminus of NRas, which is where the lipid anchors are found.
Insights
NRas proteins cluster on cell membranes by interacting with cholesterol-rich domains. Simulations show NRas proteins reduce the line tension between membrane domains, slowing their growth.
Area of Science:
- Biophysics
- Cell Biology
- Computational Biology
Background:
- Ras proteins are key regulators of cell signaling pathways.
- Ras proteins are believed to cluster in cholesterol-rich membrane nanodomains.
- The precise mechanisms of Ras protein clustering and membrane domain interaction are not fully understood.
Purpose of the Study:
- To investigate the effect of NRas protein on lipid bilayer domain formation and growth.
- To understand how NRas proteins interact with cholesterol-rich membrane domains.
- To elucidate the role of NRas in regulating membrane organization.
Main Methods:
- Coarse-grained molecular dynamics simulations of a three-component lipid bilayer.
- Simulations included a large bilayer with and without NRas proteins.
- Analysis involved techniques adapted from image processing.
Main Results:
- NRas proteins preferentially localized at the interface between lipid domains.
- The presence of NRas proteins slowed down the growth rate of these domains.
- NRas proteins were inferred to reduce the line tension between ordered and disordered membrane regions.
Conclusions:
- NRas proteins play a role in modulating membrane domain organization.
- The interaction of NRas with membrane domains influences their dynamics.
- Further research is needed to fully understand NRas C-terminus structure and lipid anchor interactions.
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