Global multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations

Abstract Weak macromolecular interactions assume a dominant role in the behavior of highly concentrated solutions, and are at the center of a variety of fields ranging from colloidal chemistry to cell biology, neurodegenerative diseases, and manufacturing of protein drugs. They are frequently measur...

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Autores principales:	Arun Parupudi, Sumit K. Chaturvedi, Regina Adão, Robert W. Harkness, Sonia Dragulin-Otto, Lewis E. Kay, Reza Esfandiary, Huaying Zhao, Peter Schuck
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e909457b3b7a460aaae039df639e78fb
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spelling	oai:doaj.org-article:e909457b3b7a460aaae039df639e78fb2021-12-02T13:34:46ZGlobal multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations10.1038/s41598-021-84946-82045-2322https://doaj.org/article/e909457b3b7a460aaae039df639e78fb2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84946-8https://doaj.org/toc/2045-2322Abstract Weak macromolecular interactions assume a dominant role in the behavior of highly concentrated solutions, and are at the center of a variety of fields ranging from colloidal chemistry to cell biology, neurodegenerative diseases, and manufacturing of protein drugs. They are frequently measured in different biophysical techniques in the form of second virial coefficients, and nonideality coefficients of sedimentation and diffusion, which may be related mechanistically to macromolecular distance distributions in solution and interparticle potentials. A problem arises for proteins where reversible self-association often complicates the concentration-dependent behavior, such that grossly inconsistent coefficients are measured in experiments based on different techniques, confounding quantitative conclusions. Here we present a global multi-method analysis that synergistically bridges gaps in resolution and sensitivity of orthogonal techniques. We demonstrate the method with a panel of monoclonal antibodies exhibiting different degrees of self-association. We show how their concentration-dependent behavior, examined by static and dynamic light scattering and sedimentation velocity, can be jointly described in a self-consistent framework that separates nonideality coefficients from self-association properties, and thereby extends the quantitative interpretation of nonideality coefficients to probe dynamics in highly concentrated protein solutions.Arun ParupudiSumit K. ChaturvediRegina AdãoRobert W. HarknessSonia Dragulin-OttoLewis E. KayReza EsfandiaryHuaying ZhaoPeter SchuckNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arun Parupudi Sumit K. Chaturvedi Regina Adão Robert W. Harkness Sonia Dragulin-Otto Lewis E. Kay Reza Esfandiary Huaying Zhao Peter Schuck Global multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations
description	Abstract Weak macromolecular interactions assume a dominant role in the behavior of highly concentrated solutions, and are at the center of a variety of fields ranging from colloidal chemistry to cell biology, neurodegenerative diseases, and manufacturing of protein drugs. They are frequently measured in different biophysical techniques in the form of second virial coefficients, and nonideality coefficients of sedimentation and diffusion, which may be related mechanistically to macromolecular distance distributions in solution and interparticle potentials. A problem arises for proteins where reversible self-association often complicates the concentration-dependent behavior, such that grossly inconsistent coefficients are measured in experiments based on different techniques, confounding quantitative conclusions. Here we present a global multi-method analysis that synergistically bridges gaps in resolution and sensitivity of orthogonal techniques. We demonstrate the method with a panel of monoclonal antibodies exhibiting different degrees of self-association. We show how their concentration-dependent behavior, examined by static and dynamic light scattering and sedimentation velocity, can be jointly described in a self-consistent framework that separates nonideality coefficients from self-association properties, and thereby extends the quantitative interpretation of nonideality coefficients to probe dynamics in highly concentrated protein solutions.
format	article
author	Arun Parupudi Sumit K. Chaturvedi Regina Adão Robert W. Harkness Sonia Dragulin-Otto Lewis E. Kay Reza Esfandiary Huaying Zhao Peter Schuck
author_facet	Arun Parupudi Sumit K. Chaturvedi Regina Adão Robert W. Harkness Sonia Dragulin-Otto Lewis E. Kay Reza Esfandiary Huaying Zhao Peter Schuck
author_sort	Arun Parupudi
title	Global multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations
title_short	Global multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations
title_full	Global multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations
title_fullStr	Global multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations
title_full_unstemmed	Global multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations
title_sort	global multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e909457b3b7a460aaae039df639e78fb
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Global multi-method analysis of interaction parameters for reversibly self-associating macromolecules at high concentrations

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