Estimating and leveraging protein diffusion on ion-exchange resin surfaces

Protein mobility at solid–liquid interfaces can affect the performance of applications such as bioseparations and biosensors by facilitating reorganization of adsorbed protein, accelerating molecular recognition, and informing the fundamentals of adsorption. In the case of ion-exchange chromatograph...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2020-03, Vol.117 (13), p.7004-7010
Main Authors: Khanal, Ohnmar, Kumar, Vijesh, Schlegel, Fabrice, Lenhoff, Abraham M.
Format: Article
Language:English
Subjects:
Affinity
Beads
Binding
Biosensors
Confocal microscopy
Dependence
Diffusion
Diffusion rate
Diffusivity
Interfaces
Ion exchange
Ion exchange resins
Ion Exchange Resins - chemistry
Ion-exchange chromatography
Ionic strength
Ions
Liquid-solid interfaces
Mass transfer
Models, Chemical
Neutron scattering
Physical Sciences
Protein transport
Proteins
Proteins - chemistry
Surface diffusion
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Summary:Protein mobility at solid–liquid interfaces can affect the performance of applications such as bioseparations and biosensors by facilitating reorganization of adsorbed protein, accelerating molecular recognition, and informing the fundamentals of adsorption. In the case of ion-exchange chromatographic beads with small, tortuous pores, where the existence of surface diffusion is often not recognized, slow mass transfer can result in lower resin capacity utilization. We demonstrate that accounting for and exploiting protein surface diffusion can alleviate the mass-transfer limitations on multiple significant length scales. Although the surface diffusivity has previously been shown to correlate with ionic strength (IS) and binding affinity, we show that the dependence is solely on the binding affinity, irrespective of pH, IS, and resin ligand density. Different surface diffusivities give rise to different protein distributions within the resin, as characterized using confocal microscopy and small-angle neutron scattering (length scales of micrometer and nanometer, respectively). The binding dependence of surface diffusion inspired a protein-loading approach in which the binding affinity, and hence the surface diffusivity, is modulated by varying IS. Such gradient loading increased the protein uptake efficiency by up to 43%, corroborating the importance of protein surface diffusion in protein transport in ion-exchange chromatography.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1921499117