Journal article
Characterizing protein-protein interactions in mAb formulations: A comparative study of kD, B22, and DLVO framework
Colloids and surfaces. A, Physicochemical and engineering aspects, Vol.728(Part 1), 138505
01/05/2026
DOI: 10.1016/j.colsurfa.2025.138505
Abstract
Understanding protein-protein interactions (PPI) is essential for ensuring the developability of monoclonal antibody (mAb) therapeutics among other applications. This study investigated PPI in three IgG1 mAbs with distinct charge and molecular weight profiles using three approaches: the diffusion interaction parameter (kD), the osmotic second virial coefficient (B22), and Derjaguin-Landau-Verwey-Overbeek (DLVO) modeling. Light scattering measurements were performed to obtain kD and B22 values across a range of total ionic strengths (7.5–160 mM) and DLVO modeling was applied to decompose the total interaction energy into van der Waals attraction and electrostatic double-layer repulsion. While each method provided unique insight into PPI, results revealed distinct interaction profiles for each mAb and highlighted the limitations of using a single metric to interpret complex PPI behavior. kD captured the combined effects of thermodynamic interactions and hydrodynamic drag, while B22 quantified net thermodynamic interactions independent of hydrodynamics. DLVO modeling further enabled mechanistic interpretation by estimating the magnitude and range of attractive and repulsive forces, as well as identifying energy barriers and secondary energy minima indicative of reversible interaction. The orthogonal use of these tools revealed discrepancies between hydrodynamic and thermodynamic interactions, particularly at high ionic strengths, and helped explain nonlinear diffusion trends. Taken together, our findings demonstrate that combining kD, B22, and DLVO modeling as accessible biophysical characterization tools enables a more robust assessment of colloidal behavior, enhancing early-stage screening of mAbs for developability risks such as aggregation, high viscosity, or self-association.
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•kD, B22, and DLVO offer orthogonal insights into mAb interactions.•DLVO reveals how force components vary with ionic strength and intermolecular distance.•DLVO identifies a secondary energy minimum explaining mAb diffusion trend.•Complementary metrics resolve conflicting interpretations of PPI data.
Details
- Title: Subtitle
- Characterizing protein-protein interactions in mAb formulations: A comparative study of kD, B22, and DLVO framework
- Creators
- Parham Parnian - University of Iowa, Pharmaceutical Sciences and Experimental TherapeuticsMark A. Arnold - University of IowaReza Nejadnik - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, USA
- Resource Type
- Journal article
- Publication Details
- Colloids and surfaces. A, Physicochemical and engineering aspects, Vol.728(Part 1), 138505
- DOI
- 10.1016/j.colsurfa.2025.138505
- ISSN
- 0927-7757
- eISSN
- 1873-4359
- Publisher
- Elsevier B.V
- Grant note
- National Science Foundation: 2242763
This work is supported by the National Science Foundation under Award No.2242763.
- Language
- English
- Electronic publication date
- 09/30/2025
- Date published
- 01/05/2026
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Center for Biocatalysis and Bioprocessing; Fraternal Order of Eagles Diabetes Research Center; Chemistry
- Record Identifier
- 9985014874102771
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