AI 中文总结
研究细胞中超分子结构自组装在低目标数下受随机波动影响的问题,通过最小两隔室模型随机模拟,发现延迟促进组装易发生随机产率灾难,限制较大结构交换可恢复产率,揭示随机顺序竞争慢事件是其特征。
AI 中文摘要
细胞中超分子结构的自组装以及合成应用通常在不利的生化条件下进行,最终目标结构的拷贝数较低。不同反应性的耦合反应隔室进行空间组织(延迟促进组装)在平均场水平可提高产率,但对低目标数下随机波动的鲁棒性不明。通过最小两隔室模型的随机模拟表明,延迟促进组装在低目标数时易受随机产率灾难影响,即便单个隔室能高产组装,它们之间缓慢交换会使最终产率大幅下降。机制追溯到特定组装阶段,亚基和部分完成结构的限速交换事件的随机顺序决定了生产性生长与过量成核的比例。限制较大结构的交换可恢复大部分产率。二维六边形亚基和胞质溶胶 - 膜几何结构也有相同现象。结果表明高目标数下组装策略的成功不意味着低目标数下也成功,随机顺序发生的竞争慢事件是随机产率灾难的常见特征。
英文摘要
Self-assembly of supramolecular structures in cells and synthetic applications often proceeds under unfavorable biochemical conditions and at low copy numbers of final target structures, ranging from tens of bacterial microcompartments to a single bacterial flagellum per cell. Spatial organization through coupled reaction compartments of different reactivity (delay-facilitated assembly) can recover high yield in such environments at the mean-field level, but its robustness to stochastic fluctuations at low target numbers is unclear. Using stochastic simulations of a minimal two-compartment model, we show that delay-facilitated assembly is susceptible to a stochastic yield catastrophe at low target numbers: even when each compartment in isolation allows for high-yield assembly, slow exchange between them induces a substantial drop in the final yield. We trace the mechanism to a specific assembly stage, where the random order of rate-limiting exchange events of subunits and partially completed structures determines the ratio of productive growth to excess nucleation. Restricting the exchange of larger structures -- either by suppressing it entirely or letting exchange rates decrease with size -- restores most of the yield without altering the mean-field behavior. The same phenomenology appears for two-dimensional hexagonal subunits and in a cytosol-membrane geometry, where diffusion-limited exchange naturally implements the required size dependence. Our results show that equal success of assembly strategies at high target numbers does not imply their equal success at low target numbers, and that competing slow events occurring in random order are a common signature of stochastic yield catastrophes.
Comments17 pages, 10 figures