Application of a Simple Short-Range Attraction and Long-Range Repulsion Colloidal Model toward Predicting the Viscosity of Protein Solutions
Application of a Simple Short-Range Attraction and Long-Range Repulsion Colloidal Model toward Predicting the Viscosity of Protein Solutions
复制标题
应用简单的短程吸引和长程排斥胶体模型来预测蛋白质溶液的粘度
DOI：
10.1021/acs.molpharmaceut.2c00582
复制
发表时间：
2022
影响因子：
4.9
通讯作者：
Underhill, Patrick T.
中科院分区：
文献类型：
--
作者：
Virk, Sabitoj Singh;Underhill, Patrick T.
一些硬球胶体模型因无法准确预测蛋白质等复杂生物分子的溶液粘度而受到批评。竞争性短程吸引力和长程排斥，也称为短程吸引力和长程排斥 (SALR) 相互作用，被认为会影响低至中等离子强度下蛋白质溶液的微观结构。然而，这种相互作用主要涉及引起相变、蛋白质凝胶化或可逆簇形成，并且它们对蛋白质溶液粘度变化的影响尚未完全了解。在这项工作中，我们展示了具有 SALR 相互作用的硬球胶体模型在预测稀释至半稀释蛋白质溶液的粘度方面的应用。对以前的胶体模型无法解释的球状白蛋白和 Y 形治疗性单克隆抗体进行了比较。模型预测表明，正是吸引力和排斥力之间的耦合产生了观察到的溶液粘度随 pH、浓度和离子强度变化的实验趋势。模型的参数是通过测量第二维里系数和净表面电荷/zeta 电位获得的，无需额外拟合粘度。
Some hard-sphere colloidal models have been criticized for inaccurately predicting the solution viscosity of complex biological molecules like proteins. Competing short-range attractions and long-range repulsions, also known as short-range attraction and long-range repulsion (SALR) interactions, have been thought to affect the microstructure of a protein solution at low to moderate ionic strength. However, such interactions have been implicated primarily in causing phase transition, protein gelation, or reversible cluster formation, and their effect on protein solution viscosity change is not fully understood. In this work, we show the application of a hard-sphere colloidal model with SALR interactions toward predicting the viscosity of dilute to semi-dilute protein solutions. The comparison is performed for a globular-shaped albumin and Y-shaped therapeutic monoclonal antibody that are not explained by previous colloidal models. The model predictions show that it is the coupling between attractions and repulsions that gives rise to the observed experimental trends in solution viscosity as a function of pH, concentration, and ionic strength. The parameters of the model are obtained from measurements of the second virial coefficient and net surface charge/zeta-potential, without additional fitting of the viscosity.