This newly discovered cellular structure could be a cellular "computer."

An emerging field explores how intracellular molecular clusters come together, like the way

In human cells, "liquid-liquid phase separation" occurs because similar macromolecules are separated from the more diluted parts of the liquid cell and aggregate into dense droplets

In addition, in the cells of patients with neurodegenerative diseases, including those with Alzheimer's disease, abnormally agglutinated molecular groups in droplets are almost always present

The researchers likened polycondensites to microprocessors with built-in circuitry, as both were able to identify and calculate responses

To address this challenge, researchers at NYU Grossman School of Medicine and the German Center for Neurodegenerative Diseases have built an artificial system that reveals how the formation of condensate alters the behavior at the molecular level of enzymes called kinases, an example

The new analysis, published Sept.

"Our findings suggest that physical changes like crowding can drive the formation of congeals and convert them into biochemical signals, just as coagulants are slimy computers," said

In the study, it was found that the more active kinase in a crowded, concentrated environment is cyclin-dependent kinase 2, which is known to phosphorylate the microtubule-binding protein Tau

"Our experiments show that the formation of more Tau polypolymers drives more Tau phosphorylation," adds Holt, who is also a faculty member

Specifically, the study found that phosphorylation of a group of Alzheimer's disease-related sites (AT8 epitopes) on Tau protein accelerated threefold when Tau protein and cyclin-dependent kinases accluded into dense droplets

Work on a biosensor

To design useful versions of these computers, the team tested several artificial polycondensoles and synthesized different scaffold molecules to see which one best pulled the sample kinases — MAPK3, Fus3, and cyclin-dependent kinase 1 (Cdk1) — and their goals to increase signaling

The study also found that the formation of condensate phosphorylated a wider variety of molecules by the containing kinase and did not require the molecular shapes

Next, the research team seeks to build on a past study in Holt's lab that found that a protein complex called mTORC1 controls molecular crowding by determining the number of ribosomes, which are "machines"

Finally, the researchers also hope that their findings will advance the design

Condensed-Phase Signaling Can Expand Kinase Specificity and Respond to Macromolecular Crowding