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bioRxiv · 10.1101/2023.09.12.557452

Valency of Ligand-Receptor Binding Ignored by Pair Potentials

Morton, W.·Angioletti-Uberti, S.·Vacha, R.
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Abstract

Molecular dynamics simulations have been crucial for investigating the dynamics of nanoparticle uptake by cell membranes via ligand-receptor interactions. Use of coarsegrained models has enabled evaluation of the effects of nanoparticle size, shape, ligand distribution on nanoparticles surface, or used thoroughly in the past decade, where a percentage of lipid heads, receptors, are attracted to sites on the nanoparticle surface, ligands. However, when pair-potentials are used to represent ligand-receptor interactions, the number of receptors interacting with one ligand, valency, may vary. We demonstrate that the curvature of a nanoparticle, strength of ligand-receptor interactions, and ligand or receptor concentration change the valency - ranging from 3.4 to 5.1 in this study. Such change in valency can create inaccurate comparisons between nanoparticles, or even result in the uptake of smaller nanoparticles than would be expected. To rectify this inconsistency we propose the adoption of a model based on bond-formation and use it to determine the extent to which previous studies may have been effected. This work recommends avoiding pair-potentials for modeling ligandreceptor interactions to ensure methodological consistency in nanoparticle studies. TOC GraphicA rendering of a ligand coated nanoparticle coming into contact with a lipid bilayer membrane. The receptor in the membrane is highlighted for clarity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/557452v3_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@10730a2org.highwire.dtl.DTLVardef@109f0b9org.highwire.dtl.DTLVardef@19b0d80org.highwire.dtl.DTLVardef@93557a_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Morton, W., Angioletti-Uberti, S., Vacha, R.. 2023-09-15. Valency of Ligand-Receptor Binding Ignored by Pair Potentials. https://doi.org/10.1101/2023.09.12.557452

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