Enzymatic reactions: researchers reveal a regulatory mechanism by which life is controlled and organized

Process leading to CIPS. (a) Enzymes convert substrate to product through a fueled catalytic reaction, while product converts spontaneously to substrate. (b) The catalyzed reaction creates substrate and product gradients around the enzyme-rich regions, which attract more enzymes when the off-diagonal transport coefficients coupling the enzyme fluxes to the product and substrate thermodynamic forces satisfy D_pe>D_to. Credit: Physical examination letters (2022). DOI: 10.1103/PhysRevLett.129.158101

Inside cells, molecular droplets form defined compartments for chemical reactions. Not only sticky interactions between molecules, but also dynamic reactions can form such droplets, as researchers from the Max Planck Institute for Dynamics and Self-Organization (MPI-DS) and the University of Oxford. They revealed a new regulatory mechanism by which life is controlled and organized.

Traditionally, membrane-defined cellular organelles have been considered the functional units of a cell. In recent years, it has also been demonstrated that the molecular droplets formed inside the cell provide a microenvironment for important reactions. Such droplets are not surrounded by a membrane and come from phase separation. Therefore, they form dynamically and can be regulated according to the needs of the cell.

Off-balance workouts can induce droplet formation

In the Living Matter Physics Department, Director General Ramin Golestanian and his colleagues aim to reveal the organizing principles of living matter. “Until now, the formation of droplets in cells has been attributed to attractive and sticky interactions between molecules, similar to the formation of droplets in non-living equilibrium systems, such as oil droplets in salad dressing. “, explains Jaime Agudo-Canalejo, group leader at MPI-DS.

“We have now discovered that the out-of-equilibrium drive provided by the enzyme reactions can cause enzyme-rich droplets to form, even without any sticky effects. Instead, the enzymes are pushed against each other by the chemical flows they create,” he continues.

Researchers explored this new mechanism by formulating a model in which the effect of a multicomponent enzymatic reaction on the microenvironment is described. They also considered the underlying feedback mechanism through which the induced phase separation can in turn affect the initial enzymatic reaction.

“When enzyme activity becomes too intense, phase separation occurs and acts to reduce it, providing a new form of self-regulation,” explains Matthew Cotton, first author of the study. This complex interplay of molecular interactions can provide a dynamic environment for cellular processes. Therefore, the model adds another piece to the complex puzzle of how life is able to organize itself.

The research has been published in Physical examination letters.