空间分辨的成核聚合：浓缩溶液中蛋白质聚集的自由边界模型
Spatially Resolved Nucleated Polymerization: A Free-Boundary Model of Protein Aggregation in Concentrated Solutions
AI总结：
该研究提出一个自由边界模型，将蛋白质聚集的空间组织纳入动力学，通过水平集和通量条件描述生长与凝聚，计算碰撞效率，并在多体模拟中验证了聚集速率增强。
AI中文摘要：
蛋白质聚集的动力学模型通常按大小描述群体，而不考虑空间组织或形态。我们将Lumry-Eyring成核聚合扩展为一个模型，其中单体是密度场，每个聚集体是由水平集界定的区域。生长是表面可用位点上的通量条件。凝聚是两个接触表面上的结合位点之间的反应，其速率由键合速率和接触几何决定。这些位点的可用性是界面上的场，其平衡值由Wertheim微扰理论得出。因此，碰撞效率和Fuchs稳定性比是计算得出的，而非拟合的。在充分混合的极限下，模型的空间平均值逐项满足速率方程；单体分数与八分之十千分之一一致，该差异源于将聚集体大小等同于体积。凝聚核的指数为$0.5806\pm0.0013$，而针对单克隆抗体拟合的指数为$0.600\pm0.010$。计算出的稳定性比在12$k_BT$下复现了已发表的14个条件中的13个，但仅在键合速率处于其范围上限时。在多体盒子中，聚集体合并速率是两体速率的2.2至3.8倍。
英文摘要：
Kinetic models of protein aggregation describe populations by size, not by spatial organization or morphology. We extend Lumry-Eyring nucleated polymerization to a model in which the monomer is a density field and each aggregate is a region bounded by a level set. Growth is a flux condition on the available sites of a surface. Condensation is a reaction between the bonding sites of two surfaces in contact, at a rate set by the bond rate and the contact geometry. The availability of those sites is a field on the interface, and its equilibrium value follows from Wertheim's perturbation theory. The collision efficiency and the Fuchs stability ratio are therefore computed, not fitted. In a well-mixed limit the model's spatial averages satisfy the rate equations term by term; the monomer fraction agrees to eight parts in ten thousand, a difference that arises from equating aggregate size with volume. The condensation kernel's exponent is $0.5806\pm0.0013$ against the $0.600\pm0.010$ fitted to a monoclonal antibody. The computed stability ratio reproduces thirteen of fourteen published conditions at twelve $k_BT$, but only with the bond rate at the top of its range. In a many-body box, aggregates merge at $2.2$ to $3.8$ times the two-body rate.
