Cells organize many of their most important activities using structures known as biomolecular condensates. Unlike traditional compartments in the cell, these droplet-like clusters are not enclosed by membranes. They help control how genetic instructions in DNA are converted into proteins, assist in clearing away cellular waste that could otherwise become toxic, and can even play a role in suppressing tumor growth. Because condensates behave like liquids that can fuse, flow, and quickly exchange components, scientists long believed they were simple, unstructured droplets.
Research published in Nature Structural and Molecular Biology on February 2, 2026, challenges that long-standing view. A team at Scripps Research found that some condensates are not random blobs at all. Instead, they are built from complex networks of thin, thread-like protein filaments. These internal frameworks give the droplets a defined architecture that is crucial for how they work. The discovery points to new strategies for treating diseases such as cancer and neurodegenerative disorders.
“Ever since we realized that disruptions in condensate formation are at the heart of many diseases, it has been challenging to target them therapeutically because they appeared to lack structure — there were no specific features for a drug to latch onto,” says Keren Lasker, associate professor at Scripps Research and senior author of the study. “This work changes that. We can now see that some condensates have an internal architecture, and that, importantly, this structure is required for function, opening the door to targeting these membrane-less assemblies much like we target individual proteins.”
Zooming In on the PopZ Protein
To explore how condensates can act like compartments without membranes, Lasker’s lab examined a bacterial protein called PopZ. In certain rod-shaped bacteria, PopZ gathers at the cell poles (the rounded ends of the cell), forming condensates that organize other proteins needed for cell division.
Working closely with Scripps Research professor Ashok Deniz and assistant professor Raphael Park, who co-led the study, the team used cryo-electron tomography (cryo-ET). This imaging method functions much like a CT scan at the molecular scale, allowing researchers to see cellular structures in remarkable detail. The images revealed that PopZ proteins assemble into filaments through a carefully ordered, step-by-step process. These filaments then form a scaffold that determines the condensate’s physical characteristics.
Protein Shape Changes Inside Condensates
The researchers went further to examine how individual PopZ molecules behave. Using single-molecule Förster resonance energy transfer (FRET), a technique that detects tiny shifts in distance within proteins by measuring energy transfer between fluorescent tags, they discovered that PopZ changes shape depending on its location. The protein adopts one conformation outside a condensate and a different one inside it.
“Realizing that protein conformation depends on location gives us multiple ways to engineer cellular function,” says Daniel Scholl, first author and former postdoctoral researcher in the Lasker and Deniz labs.
Why Filament Structure Is Essential
To test whether the filaments were merely structural details or actually necessary for life, the team engineered a mutant version of PopZ that could no longer form filaments. The altered condensates became much more fluid and had lower surface tension. When these changes were introduced into living bacteria, the cells stopped growing and failed to properly separate their DNA. This showed that the condensate’s physical properties, not just its chemical ingredients, are vital for normal cellular function.
Implications for Cancer and Neurodegenerative Disease
Although the experiments focused on bacteria, the findings have broader relevance. In human cells, filament-based condensates carry out two major tasks: clearing away damaged or toxic proteins and controlling cell growth. If the cleanup condensates break down, harmful proteins can build up, which is a defining feature of neurodegenerative diseases such as ALS. If growth-regulating condensates fail, the protective mechanisms that prevent tumors can collapse, contributing to cancers including prostate, breast and endometrial.
“By demonstrating that condensate architecture is both definable and functionally critical, the work raises the possibility of designing therapies that act directly on condensate structure and correct the underlying disorganization that allows disease to take hold,” says Lasker.
In addition to Lasker, Scholl, Deniz, and Park, authors of the study, “The filamentous ultrastructure of the PopZ condensate is required for its cellular function,” include Tumara Boyd, Andrew P. Latham, Alexandra Salazar, Asma Khan, Steven Boeynaems, Alex S. Holehouse, Gabriel C. Lander and Andrej Sali.
The research was supported by the National Institutes of Health (NINDS DP2 NS142714, NIGMS F32 GM150243, NIGMS R01 GM083960, NINDS R01 NS095892, NIGMS RO1 GM14305, NIGMS R35 GM130375, and ORIPS10 OD032467), the National Science Foundation (2235200 and DBI 2213983), the Water and Life Interface Institute, the Gordon & Betty Moore Foundation (Moore Inventor Fellowship 579361), and the Cancer Prevention and Research Institute of Texas (RR220094).
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