Volume 169, 2014

NRas slows the rate at which a model lipid bilayer phase separates


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.

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Article information

Article type
12 Dec 2013
26 Feb 2014
First published
27 Feb 2014
This article is Open Access
Creative Commons BY license

Faraday Discuss., 2014,169, 209-223

Author version available

NRas slows the rate at which a model lipid bilayer phase separates

E. Jefferys, M. S. P. Sansom and P. W. Fowler, Faraday Discuss., 2014, 169, 209 DOI: 10.1039/C3FD00131H

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