Recapitulation of cell-like KRAS4b membrane dynamics on complex biomimetic membranes

Rebika Shrestha; De Chen; Peter Frank; Dwight V Nissley; Thomas J Turbyville

doi:10.1016/j.isci.2021.103608

Recapitulation of cell-like KRAS4b membrane dynamics on complex biomimetic membranes

iScience. 2021 Dec 10;25(1):103608. doi: 10.1016/j.isci.2021.103608. eCollection 2022 Jan 21.

Authors

Rebika Shrestha¹, De Chen¹, Peter Frank¹, Dwight V Nissley¹, Thomas J Turbyville¹

Affiliation

¹ NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA.

Abstract

Understanding the spatiotemporal distribution and dynamics of RAS on the plasma membrane (PM) is the key for elucidating the molecular mechanisms of the RAS signaling pathway. Single particle tracking (SPT) experiments show that in cells, KRAS diffuses in at least three interchanging states on the cellular PM; however, KRAS remains monomeric and always shows homogeneous diffusion on artificial membranes. Here, we show for the first time on a supported lipid bilayer composed of heterogeneous lipid components that we can recapitulate the three-state diffusion of KRAS seen in cells. The use of a biologically relevant eight-lipid system opens a new frontier in the biophysical studies of RAS and other membrane associated proteins on a biomimetic system that recapitulates the complexity of a cellular PM.

Keywords: Biomimetics; Biophysics; Biotechnology; Membrane architecture; Molecular biology.