Peking University Researchers Capture Real-Time Evolution of Protein Clusters Using Advanced Nano-Imaging Technology

Scientists use liquid-phase electron microscopy to reveal how proteins form clusters, offering new insights into neurodegenerative disease and cell biology.

By: AXL Media

Published: Apr 25, 2026, 8:04 AM EDT

Source: Information for this report was sourced from EurekAlert!

Nano-Scale Breakthrough Challenges Traditional Biological Nucleation Theory

The microscopic journey from individual protein molecules to complex cellular structures has long remained an observational mystery, but recent findings from Peking University have illuminated these critical early stages. By employing Liquid-phase Transmission Electron Microscopy, or LP-TEM, researchers captured the transition of intrinsically disordered proteins from simple oligomers into networked clusters. This discovery suggests that the formation of these biological structures does not follow the traditional Classical Nucleation Theory, instead operating through a multi-step, non-classical mechanism. According to the research team, this visualization provides a missing link in understanding how proteins organize themselves within the crowded environment of a living cell.

Visualizing the Hidden Dynamics of Membraneless Organelles

Intrinsically disordered proteins and regions, known as IDPs and IDRs, play a dual role in human biology, facilitating essential biochemical reactions through liquid-liquid phase separation while also posing risks through toxic aggregation. The study focused on the low-complexity domain of the Fused in Sarcoma protein, which was encapsulated in a graphene liquid cell to maintain its native solution state. This method allowed for millisecond temporal resolution, enabling the team to watch as individual "stickers" on protein chains interacted to form molecular assemblies. These assemblies eventually reached a specific concentration threshold, triggering a transition into a dense phase that serves as the foundation for membraneless organelles.

The Role of Molecular Dynamics in Structural Mapping

The precision of the study relied heavily on a multi-disciplinary approach involving theoretical chemistry and advanced computational modeling. Professor Yiqin Gao and researcher Yihao Niu provided critical molecular dynamics simulations that allowed the team to interpret the conformational ensembles of the proteins observed via electron microscopy. By matching real-time imagery with simulated data, the researchers could identify how "spacer" sequences between protein stickers influence the fluidity and density of the resulting clusters. This synergy between physical observation and theoretical modeling confirmed that clusters exist even in solutions that were...