AI 中文总结
本研究开发耦合相分离、分子切换与动态交联的瞬态网络模型及连续介质框架，揭示了分子构象切换与动态交联调控凝聚物老化及形态转变的力学机制。
AI 中文摘要
生物分子凝聚物会发生显著变化，例如因生化环境变化导致分子相互作用改变，进而从类液态转变为类凝胶或类固体聚集体。分子相互作用的改变如何引发凝聚物材料属性与空间组织的此类转变，这一问题尚未得到阐明。为解决该问题，我们将生化环境表示为包含类液态富蛋白相、类网络状富蛋白相及溶剂的三相混合物。因生化环境变化，蛋白分子可在两种构象状态间可逆切换；切换后的构象状态下，分子的交联结构域暴露，会促进相分离状态中瞬态网络的形成。我们开发了瞬态网络模型与连续介质框架，将相分离、分子切换及动态交联耦合，以预测凝聚物的形态与力学特性。该瞬态网络模型预测，非老化网络表现如麦克斯韦流体；当网络通过交联稳定缓慢老化时，呈现类麦克斯韦行为及依赖等待时间的弛豫；而高度老化的网络则表现出类似开尔文-沃伊特固体的弹性回复。我们的耦合连续介质模型表明，网络形成中分子切换与动态交联的相互作用塑造了凝聚物相的空间组织。综上，本研究阐明了构象切换与分子交联如何调控凝聚物材料属性与形态的机制路径。
英文摘要
Biomolecular condensates can undergo striking changes, such as transitioning from a liquid-like to a gel- or a solid-like aggregate due to changes in molecular interactions in response to changes in the biochemical environment. The question of how modified molecular interactions lead to such a transition in the material properties and spatial organization of condensates has not yet been elucidated. To address this question, we represent the biochemical environment as a triphasic mixture comprising a liquid-like protein-rich phase, a network-like protein-rich phase, and solvent. Owing to a change in the biochemical environment, protein molecules can reversibly switch between two conformational states. In a switched conformational state, the cross-linking domains of molecules are exposed which promote transient network formation in phase separated states. We develop a transient-network model and a continuum framework that couples phase separation, molecular switching, and dynamic cross-linking to predict condensate morphology and mechanics. The transient-network model predicts that a non-aging network behaves like a Maxwell fluid. When a network slowly ages via stabilization of cross-links, it shows Maxwell-like behavior and waiting time-dependent relaxation. However, a strongly aged network shows elastic recoil like characteristic of a Kelvin-Voigt solid. Our coupled continuum model demonstrates that the interplay of molecular switching and dynamic cross-linking in network formation shapes the spatial organization of condensate phases. In summary, this work demonstrates a mechanistic route explaining how conformational switching and molecular cross-linking regulate material properties and morphology of condensates.
