Electron Videography of a Lipid–Protein Tango

• DOI: 10.1101/2022.11.13.516315
• Publication Date: 2022-11-14T15:31:37Z
• Authors: John W. Smith; Lauren N. Carnevale; Aditi Das; Qian Chen
• Keywords: Nanodisc; Videography; Biomolecule

Biological phenomena ranging from enzymatic catalysis to synaptic transmission find their origins in the morphological fluctuations of biomolecules and biomolecular assemblies liquid water. However, directly imaging these nanoscopic dynamics without probes or labels has been a fundamental methodological challenge. Here we developed an approach for ‘molecular videography’—combining liquid-phase electron microscopy with molecular modelling—with which filmed nanoscale individual, freely suspended, unlabelled membrane protein nanodiscs liquid. These unprecedented observations enabled us quantify fingerprints lipid–protein interactions directly, revealing that nanodisc shape undulations are defined by mechanics encircling scaffold proteins, whereas lipid reach across surprisingly long ranges delineate dynamically modified domains increase stability. Overall, this work illustrates experimental image, quantify, understand at nanometre scale.