4D Liquid-phase Electron Microscopy of Ferritin by Brownian Single Particle Analysis

TL;DR

This paper introduces Brownian single particle analysis (BSPA), a method using liquid phase electron microscopy to study protein dynamics in real-time, significantly reducing data acquisition time and revealing conformational and hydration changes.

Contribution

The paper presents BSPA, a novel approach combining liquid phase electron microscopy with single particle analysis to enable dynamic, real-time structural studies of proteins.

Findings

Reduces data acquisition time from hours to seconds.

Allows observation of conformational changes and hydration dynamics.

Opens new possibilities for dynamic structural biology.

Abstract

Protein function and activity are a consequence of its three-dimensional structure. Single particle analysis of cryogenic electron micrographs has radically changed structural biology allowing atomic reconstruction of almost any type of proteins. While such an approach provides snapshots of three-dimensional structural information that can be correlated with function, the new frontier of protein structural biology is in the fourth dimension, time. Here we propose the use of liquid phase electron microscopy to expand structural biology into dynamic studies. We apply here single particle analysis algorithm to images of proteins in Brownian motion through time; thus, Brownian single particle analysis (BSPA). BSPA enables to reduce the acquisition time from hours, in cryo-EM, to seconds and achieve information on conformational changes, hydration dynamics, and effects of thermal fluctuations. Yielding all these previously neglected aspects, BSPA may lead to the verge of a new field: dynamic structural biology.