Single molecule studies of multivalent molecular interactions enabled by plasmon-enhanced fluorescence

The interaction of macromolecules via multiple weak interactions, so called multivalency, is a key feature present throughout nature for example in the recognition of pathogens by the immune system or the activation of signaling pathways via a concentration dependent pathway. The avidity, the apparent increased binding affinity, is conceptually understood as a local concentration effect leading to enhanced rebinding of the individual binding motifs of a multivalent molecule. Here we present a plasmon enhanced fluorescence platform to study the binding and interactions of multivalent biomolecules at the single molecule level. We show increase of avidity and superselectivity of binding as the valency of the interaction is increased and extract information about the role of molecular structure in modulating the avidity with the potential to guide the design of multivalent therapeutic constructs.

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Published
2025-06-02
DOI
https://doi.org/10.1117/12.3056398
Primary Topic
Nanofabrication and Lithography Techniques
Type
article
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Single molecule studies of multivalent molecular interactions enabled by plasmon-enhanced fluorescence

Sjoerd W. Nooteboom, Duncan Stewart Sutherland, Peter Zijlstra, Kasper R. Okholm
Nanofabrication and Lithography Techniques
article

Single molecule studies of multivalent molecular interactions enabled by plasmon-enhanced fluorescence

Sjoerd W. Nooteboom, Duncan Stewart Sutherland, Peter Zijlstra, Kasper R. Okholm
article en

Abstract

The interaction of macromolecules via multiple weak interactions, so called multivalency, is a key feature present throughout nature for example in the recognition of pathogens by the immune system or the activation of signaling pathways via a concentration dependent pathway. The avidity, the apparent increased binding affinity, is conceptually understood as a local concentration effect leading to enhanced rebinding of the individual binding motifs of a multivalent molecule. Here we present a plasmon enhanced fluorescence platform to study the binding and interactions of multivalent biomolecules at the single molecule level. We show increase of avidity and superselectivity of binding as the valency of the interaction is increased and extract information about the role of molecular structure in modulating the avidity with the potential to guide the design of multivalent therapeutic constructs.

Aarhus University (DK), Eindhoven University of Technology (NL)
Openalex Percentile: Top 89%
Nanofabrication and Lithography Techniques
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