No ordinary proteins: Adsorption and molecular orientation of monoclonal antibodies.


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
Aug 2021
Historique:
received: 07 01 2021
accepted: 07 07 2021
entrez: 28 8 2021
pubmed: 29 8 2021
medline: 29 8 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34452912
pii: 7/35/eabg2873
doi: 10.1126/sciadv.abg2873
pmc: PMC8397265
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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Auteurs

Ankit Kanthe (A)

Department of Chemical Engineering, The City College of New York, New York, NY 10031, USA.

Andrew Ilott (A)

Drug Product Development, Bristol Myers Squibb, New Brunswick, NJ 08901, USA.

Mary Krause (M)

Drug Product Development, Bristol Myers Squibb, New Brunswick, NJ 08901, USA.

Songyan Zheng (S)

Drug Product Development, Bristol Myers Squibb, New Brunswick, NJ 08901, USA.

Jinjiang Li (J)

Pharmaceutical Development, Wolfe Laboratories, Watertown, MA, 01801, USA.

Wei Bu (W)

NSF's ChemMatCARS, Center for Advanced Radiation Sources, University of Chicago, Chicago, IL 606371, USA.

Mrinal K Bera (MK)

NSF's ChemMatCARS, Center for Advanced Radiation Sources, University of Chicago, Chicago, IL 606371, USA.

Binhua Lin (B)

NSF's ChemMatCARS, Center for Advanced Radiation Sources, University of Chicago, Chicago, IL 606371, USA.

Charles Maldarelli (C)

Department of Chemical Engineering, The City College of New York, New York, NY 10031, USA. cmaldarelli@ccny.cuny.edu tu@ccny.cuny.edu.
Levich Institute, The City College of New York, New York, NY 10031, USA.

Raymond S Tu (RS)

Department of Chemical Engineering, The City College of New York, New York, NY 10031, USA. cmaldarelli@ccny.cuny.edu tu@ccny.cuny.edu.

Classifications MeSH