No ordinary proteins: Adsorption and molecular orientation of monoclonal antibodies

Kanthe, Ankit; Ilott, Andrew; Krause, Mary; Zheng, Songyan; Li, Jinjiang; Bu, Wei; Bera, Mrinal K.; Lin, Binhua; Maldarelli, Charles; Tu, Raymond S.

doi:10.1126/sciadv.abg2873

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

Journal Article · 26 August 2021 · Science Advances

DOI: https://doi.org/10.1126/sciadv.abg2873 · OSTI ID:1825761

^[1]; Ilott, Andrew ^[2];

^[2]; Zheng, Songyan ^[2];

^[3];

^[4];

^[5];

^[1]

City College of New York, NY (United States). Dept. of Chemical Engineering
Bristol Myers Squibb, New Brunswick, NJ (United States). Drug Product Development
Wolfe Laboratories, Watertown, MA (United States). Pharmaceutical Development
Univ. of Chicago, IL (United States). NSF’s ChemMatCARS. Center for Advanced Radiation Sources
City College of New York, NY (United States). Dept. of Chemical Engineering. Levich Inst.

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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1825761

Journal Information:: Science Advances, Journal Name: Science Advances Journal Issue: 35 Vol. 7; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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