Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, OX1 3QZ, UK.
Dept. of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
Soft Matter. 2023 Nov 22;19(45):8706-8716. doi: 10.1039/d3sm00820g.
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. Notably, we uncover a detrimental impact of increased protein net charge on the surface tension of Ddx4 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 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.
液态富含蛋白质的生物分子凝聚物的表面张力是一种新兴的物理原理,控制着生物细胞的介观内部组织。在这项研究中,我们提出了一种通过简单的悬滴测量毛细长度和凝聚物密度来评估模型生物分子凝聚物表面张力的方法。我们的方法避免了以前报道的技术中需要表征凝聚物粘度的要求。我们使用由两种无序蛋白 Ddx4 的突变体组成的模型凝聚物来证明这种方法。值得注意的是,我们发现增加蛋白质净电荷对 Ddx4 凝聚物表面张力有不利影响。此外,我们还探索了 Scheutjens-Fleer 理论的应用,通过使用 Flory-Huggins 相互作用参数的自洽平均场框架计算凝聚物表面张力。这种相对简单的理论在预测 Ddx4 凝聚物表面张力方面具有半定量的准确性,并能够评估凝聚物表面的分子组织。我们的发现揭示了生物分子凝聚物中流体-流体界面的分子细节。