Yang Sean, Banerjee Priya R, Potoyan Davit A
Department of Chemistry, Iowa State University, Ames, Iowa 50011, United States.
Department of Physics, The State University of New York at Buffalo, Buffalo, New York 14260-1660,United States.
J Phys Chem B. 2024 Dec 19;128(50):12348-12357. doi: 10.1021/acs.jpcb.4c05834. Epub 2024 Dec 5.
The material properties of biomolecular condensates govern their dynamics and functions by influencing the molecular diffusion rates and biochemical interactions. A recent report has identified a characteristic timescale of temperature-dependent viscosity in biomolecular condensates arising from an activated dissociation events collectively referred to as flow activation energy. The microscopic origin of this activation energy is a complex function of sequence, stoichiometry, and external conditions. In this study, we elucidate the microscopic origins of flow activation energy in single and multicomponent condensates formed from model peptide sequences with varying "sticker" and "spacer" motifs, incorporating RNA as a secondary component. We examined how condensate density, RNA stoichiometry, and peptide sequence patterning impact these properties through detailed sequence-resolved coarse-grained simulations. Our findings reveal that flow activation energy is closely tied to the lifetime of sticker-sticker interactions under specific conditions. However, the presence of multiple competing stickers may complicate this relationship leading to frustrated interactions in condensates and lowering of activation energy. The findings of this study should help to create predictive models of material properties of condensates, which in turn can facilitate a more profound understanding of functions and programmable design principles of biomolecular condensates.
生物分子凝聚物的材料特性通过影响分子扩散速率和生化相互作用来控制其动力学和功能。最近的一份报告确定了生物分子凝聚物中与温度相关的粘度的特征时间尺度，这是由统称为流动活化能的活化解离事件引起的。这种活化能的微观起源是序列、化学计量和外部条件的复杂函数。在这项研究中，我们阐明了由具有不同“粘性”和“间隔”基序的模型肽序列形成的单组分和多组分凝聚物中流动活化能的微观起源，并将RNA作为次要组分纳入其中。我们通过详细的序列解析粗粒度模拟研究了凝聚物密度、RNA化学计量和肽序列模式如何影响这些特性。我们的研究结果表明，在特定条件下，流动活化能与粘性-粘性相互作用的寿命密切相关。然而，多个竞争性粘性物质的存在可能会使这种关系复杂化，导致凝聚物中的相互作用受挫并降低活化能。这项研究的结果应有助于创建凝聚物材料特性的预测模型，这反过来又可以促进对生物分子凝聚物的功能和可编程设计原则的更深入理解。
