Dipole-Dipole Interaction in Antibody Solutions: Correlation with Viscosity Behavior at High Concentration

PurposeThe purpose of this study was to investigate the contribution of the dipole moment to overall protein-protein interactions and viscosity of a monoclonal antibody MAb1.MethodsThe dipole moment of MAb1 was measured at various solution pH conditions using dielectric relaxation spectroscopy.ResultsThe dipole moment for MAb1 was highest at pH 6.5, and the pH dependent change in molecular dipole correlated fairly well with previously observed trends of viscosity and storage modulus versus pH. Moreover, the magnitude of the dielectric increment at pH 6.5 and 7.0 showed strong concentration dependence, indicating the presence of relatively strong dipole-dipole interactions at these pHs. To test if the cluster of charged residues present in the Fab contributes to the mean dipole moment observed for MAb1, additional mutants involving charge mutations in the CDR were investigated. In contrast to MAb1, all of the other MAbs showed significantly reduced pH and concentration dependence of the measured dipole moments and dielectric increments, respectively.ConclusionsThe solution pH dependent measured dipole moments of MAb1 appears to be in line with the observed intermolecular interactions and viscosity behavior suggesting that dipole-dipole interaction plays an important role in governing the high concentration solution behavior of this MAb.

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