Abstract
Multivalent binding is the formation of multiple, specific, distinguishable interaction pairs between two entities, such as a (nano) particle and a surface that are functionalized with complementary ligands and receptors. Multivalency combines the effects of individual interactions, it translates both the binding strength and selectivity of individual interactions ’upwards’ into the overall binding behavior. The ostensibly simple ingredients of having multiple, individually weak interactions between a particle and surface, creates complex systems with a rich and dynamic behavior. This behavior is not trivially deduced from the properties of the individual interaction motif, the particle and/or the surface, but it is based on them; we therefore call it emergent behavior.
Most of the chapters in this thesis use the influenza virus as a model system. Influenza is a roughly spherical virus that is decorated with a dense shell consisting of two types of proteins: the receptor-binding hemagglutinin (HA) and the receptor-cleaving neuraminidase (NA). HA interacts with various glycan receptors with low affinity. Influenza viruses are therefore biological, weakly multivalent nanoparticles, and they exhibit emergent behavior because of their multivalent interactions with the surfaces including cell membranes they bind to.
Three different types of emergent behavior are discussed in this thesis. Superselectivity is the strong preference of a particle to bind to a surface decorated with receptors; their coverage increases more-than-linearly with the density of receptors. Chapters 35 discuss this phenomenon and its application in a novel type of biosensor, the Multivalent Affinity Profiling chip. Recruitment refers to a particle that binds to a surface with one or more interactions, but gradually increases this number by binding additional receptors
that diffuse into the contact area. Chapter 7 uses this principle in a method aimed at determining the contact area between a particle and the surface.
The surface-bound motility of influenza virus particles is investigated in Chapter 8. Influenza is capable of moving over a surface while remaining bound, and does so while displaying density-dependent properties.
Most of the chapters in this thesis use the influenza virus as a model system. Influenza is a roughly spherical virus that is decorated with a dense shell consisting of two types of proteins: the receptor-binding hemagglutinin (HA) and the receptor-cleaving neuraminidase (NA). HA interacts with various glycan receptors with low affinity. Influenza viruses are therefore biological, weakly multivalent nanoparticles, and they exhibit emergent behavior because of their multivalent interactions with the surfaces including cell membranes they bind to.
Three different types of emergent behavior are discussed in this thesis. Superselectivity is the strong preference of a particle to bind to a surface decorated with receptors; their coverage increases more-than-linearly with the density of receptors. Chapters 35 discuss this phenomenon and its application in a novel type of biosensor, the Multivalent Affinity Profiling chip. Recruitment refers to a particle that binds to a surface with one or more interactions, but gradually increases this number by binding additional receptors
that diffuse into the contact area. Chapter 7 uses this principle in a method aimed at determining the contact area between a particle and the surface.
The surface-bound motility of influenza virus particles is investigated in Chapter 8. Influenza is capable of moving over a surface while remaining bound, and does so while displaying density-dependent properties.
| Original language | English |
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| Qualification | Doctor of Philosophy |
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| Award date | 17 Jun 2022 |
| Place of Publication | Enschede |
| Publisher | |
| Print ISBNs | 978-94-6419-522-4 |
| DOIs | |
| Publication status | Published - 17 Jun 2022 |