Single-molecule visualization of dynamic transitions of pore-forming peptides among multiple transmembrane positions.

Li, Ying; Qian, Zhenyu; Ma, Li; Hu, Shuxin; Nong, Daguan; Xu, Chunhua; Ye, Fangfu; Lu, Ying et al. · Nat Commun · 2016

basic_science · Level V

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Abstract

Research on the dynamics of single-membrane proteins remains underdeveloped due to the lack of proper approaches that can probe in real time the protein's insertion depth in lipid bilayers. Here we report a single-molecule visualization method to track both vertical insertion and lateral diffusion of membrane proteins in supported lipid bilayers by exploiting the surface-induced fluorescence attenuation (SIFA) of fluorophores. The attenuation follows a d<sup>-4</sup> dependency, where d is the fluorophore-to-surface distance. The method is validated by observing the antimicrobial peptide LL-37 to transfer among five transmembrane positions: the surface, the upper leaflet, the centre, the lower leaflet and the bottom of the lipid bilayer. These results demonstrate the power of SIFA to study protein-membrane interactions and provide unprecedented in-depth understanding of molecular mechanisms of the insertion and translocation of membrane proteins.