Here, we study interfacial systems of increasing complexity-from a single immobilized multimodal ligand to high density surfaces-to better understand how ligand behavior is affected by the presence of a surface and the presence of other ligands in the vicinity, and how this behavior scales to more » larger systems. Recently, we used molecular dynamics (MD) simulations to show that ligands immobilized on surfaces can interact and associate with neighboring ligands to form hydrophobic and charge patches, which may have important implications for the nature of protein–surface interactions. Multimodal chromatography uses multiple modes of interaction such as charge, hydrophobic, or hydrogen bonding to separate proteins.
This new understanding of multimodal surfaces has important implications for developing improved predictive models and designing new classes of multimodal separation materials. This clustering phenomenon is likely to play a key role in governing protein–surface interactions in multimodal chromatography.
CAPTO MMC IMPRES BINDING CAPACITY PATCH
Finally, we developed an approach for quantifying differences in the observed surface patterns by calculating distributions of the patch more » size and patch length. Further, the use of flexible linkers enabled hydrophobic groups to collapse to the surface, reducing their accessibility. 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. On the other hand, lowering the surface density to 1 ligand/3 nm 2 reduced or eliminated this aggregation behavior. For aggregating ligands, we report 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.
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.
CAPTO MMC IMPRES BINDING CAPACITY SERIES
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). Multimodal chromatography is a powerful tool which uses multiple modes of interaction, such as charge and hydrophobicity, to purify protein-based therapeutics.
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