[论文解读] Chemical Reactions regulated by Phase-Separated Condensates

Sudarshana Laha, Jonathan Bauermann+3 more|arXiv (Cornell University)|Mar 8, 2024

Zeolite Catalysis and Synthesis被引用 5

一句话总结

本文提出一个理论框架，将支架的相分离与稀释的参与者解耦，以研究凝结体如何调控化学反应产率和初始组装速率，并显示出用于最大效应的最佳凝结体体积。

ABSTRACT

Phase-separated liquid condensates can spatially organize and thereby regulate chemical processes. However, the physicochemical mechanisms underlying such regulation remain elusive as the intramolecular interactions responsible for phase separation give rise to a coupling between diffusion and chemical reactions at non-dilute conditions. Here, we derive a theoretical framework that decouples the phase separation of scaffold molecules from the reaction kinetics of diluted clients. As a result, phase volume and client partitioning coefficients become control parameters, which enables us to dissect the impact of phase-separated condensates on chemical reactions. We apply this framework to two chemical processes and show how condensates affect the yield of reversible chemical reactions and the initial rate of a simple assembly process. In both cases, we find an optimal condensate volume at which the respective chemical reaction property is maximal. Our work can be applied to experimentally quantify how condensed phases alter chemical processes in systems biology and unravel the mechanisms of how biomolecular condensates regulate biochemistry in living cells.

研究动机与目标

• 阐明相分离的生物分子凝聚体如何在细胞内空间性地组织反应组分。
• 建立一个框架，将支架驱动的相分离与稀释的反应参与者分开处理。
• 量化凝结体性质如何控制简单反应的产率和起始速率。

提出的方法

• 推导一个用于不可压缩混合物的连续理论，包含非稀释的支架和稀释的参与者。
• 使用具有 Onsager 互易性的迁移矩阵来描述组分之间的扩散和耦合。
• 引入交换化学势和相依活度系数，以捕捉支架–客户之间的相互作用。
• 为共存的凝结体与周围相中的稀释参与者建立反应扩散方程。
• 提供薄界面和相平衡近似，将动力学简化为可通过分配系数进行编程的参数。
• 将该框架应用于存在凝结体时的可逆反应和初始速率-dlimited 的组装过程。

Figure 1: Schematic representation of a system with dilute reacting clients in the presence of a single spherical condensate. (a) The non-dilute scaffold component can form a spherical condensate (phase I). The dilute clients (reactant and product) partition between the condensed, scaffold-rich phas

实验结果

研究问题

• RQ1 相分离的凝结体如何改变涉及稀释参与者的可逆反应的稳态产率？
• RQ2 凝结体如何影响不可逆组装过程的初始速率？
• RQ3 凝结体体积、分配系数和相特异性反应速率在调控参与者动力学中的作用是什么？
• RQ4 该框架是否能够预测能最大化反应相关性质的最佳凝结体尺寸？

主要发现

• 凝结体通过调节凝结体体积能够使可逆反应的稳态产率达到最大。
• 凝结体还能够根据相特异性扩散和反应速率来最大化组装过程的初始速率或产率。
• 该框架指出存在一个最优的凝结体体积（V^I,*），使目标反应性质达到最大。
• 相依赖的交换活度系数和分配控制稀释参与者在共存相中的分布，从而调节动力学。
• 在燃料能量驱动下偏离平衡时，出现非均匀的空间分布，增强或塑造相对于平衡条件的反应产率。

Figure 2: Schematic representation of the system to study how phase coexistence affects chemical reactions of dilute clients. (a) We consider a spherical, condensate of radius $R$ , which is rich in scaffold components (phase I ) coexisting with a scaffold-poor phase (phase II ). The system is also