Low-energy electron holographic imaging of individual tobacco mosaic virions

TL;DR

This paper demonstrates that low-energy electron holography enables non-destructive, high-resolution imaging of individual biomolecules like tobacco mosaic virions, overcoming limitations of traditional ensemble-averaging methods.

Contribution

It introduces low-energy electron holography as a novel, non-destructive technique for single-particle structural biology at nanometer resolution.

Findings

Imaged individual tobacco mosaic virions at 1 nm resolution

Revealed structural details of the virus's helical protein shell

Showed potential for Angstrom resolution imaging without radiation damage

Abstract

Modern structural biology relies on NMR, X-ray crystallography and cryo-electron microscopy for gaining information on biomolecules at nanometer, sub-nanometer or atomic resolution. All these methods, however, require averaging over a vast ensemble of entities and hence knowledge on the conformational landscape of an individual particle is lost. Unfortunately, there are now strong indications that even X-ray free electron lasers will not be able to image individual molecules but will require nanocrystal samples. Here, we show that non-destructive structural biology of single particles has now become possible by means of low-energy electron holography. As an example, individual tobacco mosaic virions deposited on ultraclean freestanding graphene are imaged at one nanometer resolution revealing structural details arising from the helical arrangement of the outer protein shell of the virus. Since low-energy electron holography is a lens-less technique and since electrons with a deBroglie wavelength of approximately 1 Angstrom do not impose radiation damage to biomolecules, the method has the potential for Angstrom resolution imaging of single biomolecules.