When Abhishek Mall and his colleagues sprayed viruses into a near-zero-humidity chamber at the European XFEL in Schenefeld, Germany, they expected to capture one static moment: the dried final state. Instead, they got a movie. Hundreds of thousands of individual snapshots revealed something scientists had only theorized before—virus protein shells don't simply shrink when they dry out. They buckle, asymmetrically, like a plastic bottle that bulges under pressure rather than collapsing uniformly.
The team, based primarily at the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg (MPSD), was studying bacteriophage MS2, an icosahedral virus—shaped like a 20-sided die—with a long history as a model system in virology. By creating an aerosol of virus-laden droplets and timing their encounter with the XFEL's ultra-bright X-ray beam, the researchers captured particles at every stage of dehydration, from fully hydrated to bone dry. The journey took just over a second.
"This was actually a good thing," said Kartik Ayyer, a group leader at MPSD. "It allowed us to reconstruct a trajectory of structural change by sorting the snapshots from fully hydrated to fully dried and anything in between."
The findings, published in the journal Light: Science & Applications, overturn a common assumption about viruses. "Many people had the impression that this capsule is like a rigid container," Ayyer said. "And this is absolutely not what we saw." In the hydrated state, MS2 capsids displayed near-perfect icosahedral symmetry. But as water molecules evaporated, the shell contracted unevenly—some regions changing before others, with deviations from that perfect geometric form becoming pronounced.
The team traced the mechanism to a flexible segment of the capsid protein called the FG loop. Molecular dynamics simulations showed that as stabilizing water molecules were lost, these loops contracted around the three-fold and five-fold pores of the capsid, creating a more compact structure. Richard Bean, a leading scientist at the SPB/SFX instrument where the research was conducted, called the finding particularly significant because it provides "direct experimental evidence for a mechanism that had previously been only theoretically predicted."
The implications stretch beyond basic biology. Understanding how viruses physically adapt to environmental stress could inform antiviral strategies and public health responses. If capsids are more mechanically adaptable than previously thought, that resilience may explain why many viruses remain infectious after traveling through air in drying droplets and then rehydrating—a pathway central to transmission.
The international collaboration brought together researchers from Germany, Sweden, the United Kingdom, Australia, Singapore, and the United States. Mall and his team say their work lays the groundwork for future studies on viral structural dynamics, with potential applications in preventing the spread of infectious disease.