Do Cellular Condensates Accelerate Biochemical Reactions? Lessons from Microdroplet Chemistry

Abstract

Cellular condensates-phase-separated concentrates of proteins and nucleic acids-provide organizational structure for biochemistry that is distinct from membrane-bound compartments. It has been suggested that one major function of cellular condensates is to accelerate biochemical processes that are normally slow or thermodynamically unfavorable. Yet, the mechanisms leading to increased reaction rates within cellular condensates remain poorly understood. In this article, we highlight recent advances in microdroplet chemistry that accelerate reaction rates by many orders of magnitude as compared to bulk and suggest that similar mechanisms may also affect reaction kinetics in cellular condensates.

Figure 1

Comparison of reactions within micro- and cellular condensates. The left schematic shows a microdroplet accelerating the production of ribose-1-phosphate from ribose and phosphate (48). The reaction is thought to be accelerated by the affinity of the polar reagents for the charged droplet interface, which localizes and orients the molecules. The right schematic depicts a cellular condensate composed of a scaffolding of multivalent RNPs. The scaffolding has a high density of enzymatic sites that interact with diffusing client molecules. The client molecules are able to readily cross the interface of the condensed phase and are more mobile in the droplet interior than the RNP scaffolding. Whereas microdroplets lose solvent through evaporation, thereby concentrating the reactants, cellular condensates exchange mass through Ostwald ripening, which could similarly have a concentrating effect. Lastly, whereas the air-water interface of the microdroplet is well defined, the interface of the cellular condensate is more diffuse and has thus far been less well-characterized. To see this figure in color, go online.