An ordinary microscope is powerless when you need to examine a single virus in detail. It's too small. But there's a tool that fires flashes billions of times brighter than sunlight — an X-ray free-electron laser. It's designed to 'photograph' a particle before the beam vaporizes it. That's how scientists studied the bacteriophage PR772, sprayed into the air.
Each image isn't a familiar picture but a pattern of spots: that's how X-rays scatter when they hit the atoms of the virus. To assemble a three-dimensional model from these patterns, the authors used rotational invariants — mathematical quantities that don't change when an object is rotated. It's like recognizing a person by their unchanging facial features, no matter the angle you look from. Comparing thousands of such 'fingerprints,' the program computed the virus's shape.
The image resolution was modest — about 20 nanometers (hundreds of times thinner than a human hair). But even so, the asymmetry of the shell and the inhomogeneity of the contents were visible. Previously, such details were lost in averaged models. Now the method allows tracking changes in viruses over time — for example, how they attach to a host cell.
as written by the authors arXiv:2606.23396
X-ray free-electron lasers (XFELs) enable diffraction-before-destruction measurements of individual nanosized bioparticles, making it possible to study the structure and dynamics of non-crystalline targets under near-biologically relevant conditions. In this work, we employ rotational invariants for model-guided and ab initio three-dimensional (3D) structure determination of aerosolized bacteriophages PR772 measured with an XFEL. The rotational invariants derived from diffraction patterns collected during multiple independent XFEL experiments facilitate the characterization of similarities and structural variations within the measured ensembles of PR772 particles. Despite modest experimental resolution, we can identify various structural features of the viruses, including the asymmetric nature of capsid distortions from the perfect icosahedral shape, density variations in the encapsulated content, and an extension at one of the capsid vertices. Rotational invariants combine structural sensitivity with applicability to forward-scattering modeling and inverse problem solving, making them powerful tools for probing the structure and temporal evolution of nano- and bioparticles using an XFEL, particularly enhancing the fidelity of structural analysis at limited experimental resolution.
An X-ray free-electron laser produces a flash lasting a few femtoseconds: that's like stretching one second to 30 million years and then taking a tiny fraction of that.
In Michael Crichton's novel 'The Andromeda Strain,' an alien virus is studied with an electron microscope and laser spectroscopy — much like in this work, except the laser didn't destroy the sample.