An intriguing aspect of the cell membrane that provokes study is lipid-anchor enrichment of lipidated proteins on the cell membrane. Specifically, recent in vitro studies involving the enrichment of Ras proteins were done to see how enrichment was affected by changes in membrane curvature. These studies demonstrated the Ras protein’s inclination to the expanded, or outer, leaflet of highly curved membranes. Other research done in vivo, however, provoked further inquiry into Ras protein behavior, since when highly curved protrusions were created in living cells, Ras proteins showed affinity for the inner leaflet. This inspired research to determine the exact mechanism (e.g. tension, curvature, lipid diffusion tendencies) affecting Ras protein spatial localization. Since mutated Ras can initiate uncontrolled cell division (cancer), this research would allow for deeper understanding of the mechanisms of the Ras protein, in order to inhibit uncontrolled signaling and binding to the cell membrane. A molecular level mean field density functional theory, discretized in space and encoded in Fortran, was used to create multiple types of model membranes and calculate the relative densities of the N-Ras protein as a function of membrane curvature, tension and concentration of lipids in the outer leaflet . The hypothesized belief was that Ras proteins adsorb to the inner leaflet more with increased tension and concentration of lipids in the outer leaflet in vivo since these factors would significantly increase the concentration of lipids in the outer leaflet; results instead proved that it is moreso the diffusion of lipids from the inner to the expanded leaflet of curved membranes that could drive a shift in the lateral pressure fields to allow more Ras protein enrichment in the inner leaflet, as seen in the in vivo experimental studies.
"The Effects of Tension, Curvature, and Lipid Diffusion on the Enrichment of Ras Proteins in Model Membranes,"
Journal of the South Carolina Academy of Science: Vol. 15
, Article 14.
Available at: https://scholarcommons.sc.edu/jscas/vol15/iss2/14