Dipole-dipole interaction in antibody solutions: correlation with viscosity behavior at high concentration

Area of Science:

• Biophysics
• Protein Chemistry

Background:

• Protein-protein interactions and solution viscosity are critical for monoclonal antibody (MAb) formulation and efficacy.
• Understanding the molecular forces governing these properties is essential for biopharmaceutical development.

Purpose of the Study:

• To investigate the role of the dipole moment in protein-protein interactions and viscosity of a specific monoclonal antibody, MAb1.
• To determine how solution pH affects the dipole moment and its correlation with MAb1's physical properties.

Main Methods:

• Dielectric relaxation spectroscopy was employed to measure the dipole moment of MAb1 across various solution pH conditions.
• Charge mutations in the complementary determining region (CDR) of MAb1 mutants were investigated to assess their contribution to the dipole moment.

Main Results:

• MAb1 exhibited a peak dipole moment at pH 6.5, correlating with viscosity and storage modulus trends.
• Strong concentration dependence of the dielectric increment at pH 6.5 and 7.0 indicated significant dipole-dipole interactions.
• MAb mutants showed reduced pH and concentration dependence compared to MAb1.

Conclusions:

• The pH-dependent dipole moment of MAb1 aligns with its intermolecular interactions and viscosity, highlighting the importance of dipole-dipole interactions.
• Dipole-dipole interactions appear to significantly influence the high-concentration solution behavior of MAb1.