ArticleBiophysical journal2014
Observation of small cluster formation in concentrated monoclonal antibody solutions and its implications to solution viscosity.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed.
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- Temperature and excipient mediated modulation of monoclonal antibody interactions revealed bymAbs · 2025Article
- Diffusion, search and attack motions of antibodies.Communications biology · 2025Article
- Cataract-Causing Mutant R188C of βB2 Crystallin With Low Structural Stability is Sensitive to Environmental Stresses and Prone to Aggregates Formation.Exploration (Beijing, China) · 2025Article
- A colloidal model for the equilibrium assembly and liquid-liquid phase separation of the reflectin A1 protein.Biophysical journal · 2024Article
- Portable Microfluidic Viscometer for Formulation Development and in Situ Quality Control of Protein and Antibody Solutions.Analytical chemistry · 2024Article
- Stability of Protein Pharmaceuticals: Recent Advances.Pharmaceutical research · 2024Review
- Testing mixing rules for structural and dynamical quantities in multi-component crowded protein solutions.APL bioengineering · 2024Article
- The viscoelasticity of high concentration monoclonal antibodies using particle tracking microrheology.APL bioengineering · 2024Article
- Combining Scattering Experiments and Colloid Theory to Characterize Charge Effects in Concentrated Antibody Solutions.Molecular pharmaceutics · 2024Article
- Antibodies Adsorbed to the Air-Water Interface Form Soft Glasses.Langmuir : the ACS journal of surfaces and colloids · 2023Article
- Enabling Efficient Design of Biological Formulations Through Advanced Characterization.Pharmaceutical research · 2023Review
- The Relationship between Protein-Protein Interactions and Liquid-Liquid Phase Separation for Monoclonal Antibodies.Molecular pharmaceutics · 2023Article
- Using Cluster Theory to Calculate the Experimental Structure Factors of Antibody Solutions.Molecular pharmaceutics · 2023Article
- Conformational Changes and Drivers of Monoclonal Antibody Liquid-Liquid Phase Separation.Journal of pharmaceutical sciences · 2023Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable mAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions.
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