No ordinary proteins: Adsorption and molecular orientation of monoclonal antibodies
| Autor: | Ankit D. Kanthe, Raymond S. Tu, Songyan Zheng, Mary Elizabeth Krause, Jinjiang Li, Mrinal K. Bera, Wei Bu, Charles Maldarelli, Andrew J. Ilott, Binhua Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Surface (mathematics)
Electron density Quantitative Biology::Biomolecules Multidisciplinary Materials science Materials Science SciAdv r-articles Dynamic Tension Quantitative Biology::Cell Behavior Condensed Matter::Soft Condensed Matter chemistry.chemical_compound Condensed Matter::Materials Science Adsorption Engineering chemistry Chemical physics Phase space Molecule Homology modeling Homology (chemistry) Physics::Chemical Physics Research Articles Research Article |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | Antibodies adsorbing to the interface are shown to dynamically reorient and unfold to define a quasi-equilibrium state. The interaction of monoclonal antibodies (mAbs) with air/water interfaces plays a crucial role in their overall stability in solution. We aim to understand this behavior using pendant bubble measurements to track the dynamic tension reduction and x-ray reflectivity to obtain the electron density profiles (EDPs) at the surface. Native immunoglobulin G mAb is a rigid molecule with a flat, “Y” shape, and simulated EDPs are obtained by rotating a homology construct at the surface. Comparing simulations with experimental EDPs, we obtain surface orientation probability maps showing mAbs transition from flat-on Y-shape configurations to side-on or end-on configurations with increasing concentration. The modeling also shows the presence of β sheets at the surface. Overall, the experiments and the homology modeling elucidate the orientational phase space during different stages of adsorption of mAbs at the air/water interface. These finding will help define new strategies for the manufacture and storage of antibody-based therapeutics. |
| Databáze: | OpenAIRE |
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