Dominant energetics in multi-component bio-molecular condensates

Abstract

The condensation of bio-molecules into membrane-less organelles has been shown to be integral to biological function and malfunction in living cells. These condensed phases typically contain many different molecular components which can all interact with each other. A fundamental challenge with such systems, therefore, is to identify and estimate out of all possible intermolecular interactions the ones which drive the process. Here we address this challenge by developing and determining from experimental data a dominance parameterDαfor each soluteαin a multi-component system. This parameter elucidates what fraction of the total free energy change upon phase separation is associated with interactions with each solute, and can be estimated using simple experimental methods. In addition, under the assumption that all solutes contribute energetically favourably to the phase separation process, the theory predicts that modulators that drive phase separation preferentially partition inside condensates, and vice versa. Our formulation does not assume a specific form of the free energy or the number of solute components, allowing the framework to be applied to study energetics in a wide range of phase separation systems.