Researchers at the Okinawa Institute of Science and Technology (OIST), working with the Max Planck Institute for Dynamics and Self-Organization (MPI-DS) and RIKEN, have found that crowding proteins together inside tiny liquid droplets can make enzymes work faster, according to Mirage News. The same study, reported on 30 October 2026, found the relationship runs both ways: busier enzymes also make the droplet liquid flow more easily.
The work addresses a gap in understanding how the physical conditions inside cells shape the molecules that carry out metabolism. Much of a cell's chemistry happens in the cytoplasm, which is not a uniform soup. Proteins and other molecules gather into compartments that lack membranes, producing local environments that are densely packed. How those conditions affect enzymes, and how enzymes might alter them in return, had received little attention.
Why it matters
Enzymes drive the reactions that keep cells alive, and many of those reactions occur in crowded, compartmentalised spaces rather than in dilute solutions. If crowding can change how quickly an enzyme works, then the physical structure of the cytoplasm is part of how metabolism is regulated, not just a backdrop to it.
The findings also suggest a feedback loop at the smallest scales. According to Mirage News, the researchers describe a two-way relationship in which protein density influences enzyme behaviour and enzyme activity, in turn, changes the movement of the surrounding liquid. Senior author Professor Paola Laurino, who leads the Protein Engineering and Evolution Unit at OIST, said the study links interactions between individual atoms to the movement of molecules across an entire droplet, with events at the smallest scales shaping and being shaped by the behaviour of a much larger system.
Testing droplets packed with protein
In the first stage of the work, the OIST team built model droplets containing a protein called BSA at a range of concentrations, from dilute mixtures to ones heavily loaded with the protein. They then introduced enzymes and their substrates into these droplets — lactate dehydrogenase in one set of experiments and alcohol dehydrogenase in another — to observe how crowding influenced catalytic activity.
The results showed that raising the BSA concentration increased enzyme activity up to a point. Only at very high BSA levels did the dense packing begin to work against the reaction, with activity falling off. Laurino noted that the initial rise was counter-intuitive, since crowding would normally be expected to hinder the movement of enzymes and substrates and thicken the liquid, slowing the reaction from the outset.
To explain the unexpected boost, researchers at RIKEN ran computer simulations tracking how the enzyme's structure shifted as the surroundings grew more crowded. In a dilute setting, the enzyme's active site — the region where substrates bind and react — was open. As BSA crowded in, that site closed. Laurino said that in the closed state the energy barrier was much lower, making the reaction proceed more readily, and that detecting this change in the simulations came as a surprise to the team.
Enzymes set the liquid in motion
The second phase of the study looked at the reverse direction: how enzyme activity affects the fluid dynamics inside the droplets. Using fluorescent tracers, the researchers observed that active enzymes allowed both BSA proteins and fluorescent nanoparticles to move more freely through the crowded droplets. Droplets holding modified, inactive enzymes were more viscous, and the molecules inside them moved more slowly.
Professor Ramin Golestanian, director of the Living Matter Physics department at MPI-DS, said the team also found that higher concentrations of enzymes or substrates in the droplets increased mobility. In a theoretical model, MPI-DS researchers proposed that enzyme activity generates chemical gradients within the droplets, which in turn drive tiny flows. Golestanian said these flows let molecules move more freely and mix inside the droplet, pointing to how enzyme activity can produce physical effects on larger scales.
Laurino's future plans include testing whether the same two-way interaction holds for multi-enzyme complexes, where several enzymes sit close together, and running experiments inside living bacterial cells to see whether the findings survive more complex biological conditions.
