Cluster Percolation Causes Shear Thinning Behavior in Concentrated Solutions of Monoclonal Antibodies

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Alfredo Lanzaro
  • Aisling Roche
  • Nicole Sibanda
  • Daniel Corbett
  • Peter Davis
  • Maryam Shah
  • Jai A. Pathak
  • Shahid Uddin
  • Christopher F. van der Walle
  • Xue-Feng Yuan

Abstract

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 3s -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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)2669-2682
Number of pages14
JournalMolecular Pharmaceutics
Volume18
Issue number7
Early online date14 Jun 2021
DOIs
Publication statusPublished - 5 Jul 2021