Formation of ligand clusters on multimodal chromatographic surfaces

Camille L. Bilodeau, Edmond Y. Lau, David Roush, Shekhar Garde, Steven M. Cramer

Research output: Contribution to journalArticle

Abstract

Multimodal chromatography is a powerful tool which uses multiple modes of interaction, such as charge and hydrophobicity, to purify protein-based therapeutics. In this work, we performed molecular dynamics simulations of a series of multimodal cation-exchange ligands immobilized on a hydrophilic self-assembled monolayer surface at the commercially relevant surface density (1 ligand/nm2). We found that ligands that were flexible and terminated in a hydrophobic group had a propensity to aggregate on the surface, while less flexible ligands containing a hydrophobic group closer to the surface did not aggregate. For aggregating ligands, this resulted in the formation of a surface pattern that contained relatively large patches of hydrophobicity and charge whose sizes exceeded the length scale of the individual ligands. On the other hand, lowering the surface density to 1 ligand/3 nm2 reduced or eliminated this aggregation behavior. In addition, the introduction of a flexible linker (corresponding to the commercially available ligand) enhanced cluster formation and allowed aggregation to occur at lower surface densities. Further, the use of flexible linkers enabled hydrophobic groups to collapse to the surface, reducing their accessibility. Finally, we developed an approach for quantifying differences in the observed surface patterns by calculating distributions of the patch size and patch length. This clustering phenomenon is likely to play a key role in governing protein-surface interactions in multimodal chromatography. This new understanding of multimodal surfaces has important implications for developing improved predictive models and designing new classes of multimodal separation materials. ©

Original languageEnglish (US)
JournalLangmuir
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Ligands
ligands
chromatography
Hydrophobicity
hydrophobicity
Chromatography
Agglomeration
proteins
Proteins
Self assembled monolayers
surface reactions
Molecular dynamics
Cations
Membrane Proteins
Ion exchange
molecular dynamics
Positive ions
cations
Computer simulation
simulation

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Spectroscopy
  • Electrochemistry

Cite this

Formation of ligand clusters on multimodal chromatographic surfaces. / Bilodeau, Camille L.; Lau, Edmond Y.; Roush, David; Garde, Shekhar; Cramer, Steven M.

In: Langmuir, 01.01.2019.

Research output: Contribution to journalArticle

Bilodeau, Camille L. ; Lau, Edmond Y. ; Roush, David ; Garde, Shekhar ; Cramer, Steven M. / Formation of ligand clusters on multimodal chromatographic surfaces. In: Langmuir. 2019.
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