标题： 结合散射实验和胶体理论表征高浓度抗体溶液中的电荷效应 显示英文标题

标题： Combining scattering experiments and colloid theory to characterize charge effects in concentrated antibody solutions

摘要： 电荷及其对蛋白质-蛋白质相互作用的贡献对于单克隆抗体（mAb）溶液的关键结构和动态特性至关重要。 事实上，它们影响表观分子量、静态结构因子、集体扩散系数或相对粘度及其浓度依赖性。 此外，电荷在mAbs的胶体稳定性中起着重要作用。 存在标准的实验工具来表征mAb的净电荷，例如测量电泳迁移率、第二维里系数或扩散相互作用参数。 然而，所得值难以直接与抗体的实际总净电荷以及基于其已知分子结构的理论预测相关联。 在此，我们报告了使用电泳测量、静态和动态光散射、小角X射线散射（SAXS）以及基于示踪粒子的微流变学结合研究的带电IgG1 mAb溶液性质的系统调查结果，作为浓度和离子强度的函数。 我们使用已建立的胶体理论和粗粒度计算机模拟分析和解释实验结果。 我们讨论了胶体模型在描述带电mAbs相互作用效应中的潜力和局限性，特别是指出了在尝试预测高浓度下的结构和动态溶液性质时，包括形状和电荷各向异性的重要性。 显示英文摘要

摘要： Charges and their contribution to protein-protein interactions are essential for the key structural and dynamic properties of monoclonal antibody (mAb) solutions. In fact, they influence the apparent molecular weight, the static structure factor, the collective diffusion coefficient or the relative viscosity and their concentration dependence. Further, charges play an important role in the colloidal stability of mAbs. There exist standard experimental tools to characterise mAb net charges such as the measurement of the electrophoretic mobility, the second virial coefficient, or the diffusion interaction parameter. However, the resulting values are difficult to be directly related to the actual overall net charge of the antibody and to theoretical predictions based on its known molecular structure. Here, we report the results of a systematic investigation of the solution properties of a charged IgG1 mAb as a function of concentration and ionic strength using a combination of electrophoretic measurements, static and dynamic light scattering, small-angle x-ray scattering (SAXS), and tracer particle-based microrheology. We analyse and interpret the experimental results using established colloid theory and coarse-grained computer simulations. We discuss the potential and limits of colloidal models for the description of interaction effects of charged mAbs, in particular pointing out the importance of incorporating shape and charge anisotropy when attempting to predict structural and dynamic solution properties at high concentrations.