Surface tension measurement and calculation of model biomolecular condensates

The surface tension of liquid-like protein-rich biomolecular condensates is an emerging physical principle governing the mesoscopic interior organisation of biological cells. In this study, we present a method to evaluate the surface tension of model biomolecular condensates, through straighforward sessile drop measurements of capillary lengths and condensate densities. Our approach bypasses the need for characterizing condensate viscosities, which was required in previously reported techniques. We demonstrate this method using model condensates comprising two mutants of the intrinsically disordered protein Ddx4(N). Notably, we uncover a detrimental impact of increased protein net charge on the surface tension of Ddx4(N) condensates. Furthermore, we explore the application of Scheutjens–Fleer theory, calculating condensate surface tensions through a self-consistent mean-field framework using Flory–Huggins interaction parameters. This relatively simple theory provides semi-quantitative accuracy in predicting Ddx4(N) condensate surface tensions and enables the evaluation of molecular organisation at condensate surfaces. Our findings shed light on the molecular details of fluid–fluid interfaces in biomolecular condensates.