Iida Yuya, Hiraide Shotaro, Miyahara Minoru T, Watanabe Satoshi
Department of Chemical Engineering, Kyoto University, Katsura, Nishikyo, Kyoto 615-8510, Japan.
J Chem Phys. 2024 Jan 28;160(4). doi: 10.1063/5.0190119.
We conducted molecular dynamics (MD) simulations in a binary Lennard-Jones system as a model system for molecular solutions and investigated the mechanism of liquid-liquid phase separation (LLPS), which has recently been recognized as a fundamental step in crystallization and organelle formation. Our simulation results showed that LLPS behavior varied drastically with the size ratio of solute to solvent molecules. Interestingly, increasing the size ratio can either facilitate or inhibit LLPS, depending on the combination of interaction strengths. We demonstrated that the unique behavior observed in MD simulation could be reasonably explained by the free energy barrier height calculated using our thermodynamic model based on the classical nucleation theory. Our model proved that the molecular size determines the change in number of interaction pairs through LLPS. Varying the size ratio changes the net number of solute-solvent and solvent-solvent interaction pairs that are either broken or newly generated per solute-solute pair generation, thereby inducing a complicated trend in LLPS depending on the interaction parameters. As smaller molecules have more interaction pairs per unit volume, their contribution is more dominant in the promotion of LLPS. Consequently, as the size ratio of the solute to the solvent increased, the LLPS mode changed from solute-related interaction-driven to solvent-related interaction-driven.
我们在二元 Lennard-Jones 系统中进行了分子动力学（MD）模拟，以此作为分子溶液的模型系统，并研究了液-液相分离（LLPS）的机制，该机制最近被认为是结晶和细胞器形成的一个基本步骤。我们的模拟结果表明，LLPS 行为会随着溶质与溶剂分子的尺寸比而急剧变化。有趣的是，增大尺寸比既可能促进也可能抑制 LLPS，这取决于相互作用强度的组合。我们证明，基于经典成核理论，使用我们的热力学模型计算出的自由能垒高度能够合理地解释 MD 模拟中观察到的独特行为。我们的模型证明，分子大小决定了通过 LLPS 产生的相互作用对数量的变化。改变尺寸比会改变每产生一对溶质-溶质对时，被破坏或新生成的溶质-溶剂和溶剂-溶剂相互作用对的净数量，从而根据相互作用参数在 LLPS 中引发复杂的趋势。由于较小的分子每单位体积具有更多的相互作用对，它们在促进 LLPS 方面的贡献更为显著。因此，随着溶质与溶剂尺寸比的增加，LLPS 模式从溶质相关相互作用驱动转变为溶剂相关相互作用驱动。
