Cluster Percolation Causes Shear Thinning Behavior in Concentrated Solutions of Monoclonal Antibodies
Cluster Percolation Causes Shear Thinning Behavior in Concentrated Solutions of Monoclonal Antibodies
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DOI：
10.1021/acs.molpharmaceut.1c00198
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发表时间：
2021-06-14
影响因子：
4.9
通讯作者：
Curtis, Robin
中科院分区：
文献类型：
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作者：
Lanzaro, Alfredo;Roche, Aisling;Curtis, Robin
高浓度（> - 100 g/L）单克隆抗体（mab）溶液通常具有异常大的溶液粘度和应变速率>= 10(3)s（-1）时的剪切变薄行为。本文采用静态、动态光散射和微流体流变学方法研究了COE-03和COE-19单克隆抗体浓溶液中蛋白-蛋白相互作用（PPIs）与流变性之间的联系。通过将实验数据与基于Baxter粘性硬球模型的预测数据进行比较，我们惊奇地发现了观察到的剪切变薄与预测的渗透阈值之间的联系。在相图的同一区域内，单抗的最长剪切松弛时间远大于模型黏性硬球，这与单抗PPIs的各向异性有关。我们的研究结果表明，不仅强度，而且短程吸引PPIs的斑块应该通过理论方法明确地解释，旨在预测致密单抗溶液的剪切速率依赖粘度。
High-concentration (>100 g/L) solutions of monoclonal antibodies (mAbs) are typically characterized by anomalously large solution viscosity and shear thinning behavior for strain rates >= 10(3) s(-1). Here, the link between protein-protein interactions (PPIs) and the rheology of concentrated solutions of COE-03 and COE-19 mAbs is studied by means of static and dynamic light scattering and microfluidic rheometry. By comparing the experimental data with predictions based on the Baxter sticky hard-sphere model, we surprisingly find a connection between the observed shear thinning and the predicted percolation threshold. The longest shear relaxation time of mAbs was much larger than that of model sticky hard spheres within the same region of the phase diagram, which is attributed to the anisotropy of the mAb PPIs. Our results suggest that not only the strength but also the patchiness of short-range attractive PPIs should be explicitly accounted for by theoretical approaches aimed at predicting the shear rate-dependent viscosity of dense mAb solutions.