Multivalency is essential for the adherence of bacteria or virus particles onto the host cell surfaces. Inhibition of these interactions can restrain the spreading of an infection by blocking the receptor at the early stages of infection. Current drug design and diagnostics are exploring the multivalency concept, i.e. binding of biological targets based on multiple weak interactions. In contrast to classical drug design relying on high-affinity inhibitors, the multivalency concept relies on commonly dendritic architectures with peripheries featuring a high density of ligands, for example, saccharides, capable of simltaneously interacting with biointerfacial receptors. In this context, the surface adaptability where ligands can diffuse laterally to optimize receptor binding is important for generating strong multivalent interactions. The topic of this project concerns Reversible Self-assembled Monolayers (rSAMs) and their applications as dynamic nanoparticle shells for multivalent interactions at biointerfaces. rSAMs are pH-switchable versions of thiol-SAMs that allow a reversible and ordered introduction of affinity reagents on sensor surfaces. Contrary to traditional SAMs of alkanethiols on gold, the rSAMs are tunable to the nature of the head group and layer order and stability, while featuring pH responsiveness and the dynamic nature of non-covalently build assemblies.
The objectives of this project were:
1) to investigate the use of rSAMs as dynamic nanoparticle shells for multivalent inhibition of pathogen infection, and
2) to assess such systems as nanoplasmonic sensors for antibody-free ultrasensitive and robust sensors for rapid in situ detection of viruses.
The project’s objectives have been largely fulfilled and advanced the state of the art in the following ways:
1) We prepared and studied a series of rSAMs layers comprising two different bioactive ligands and studied their affinity to influenza virus proteins such as neuraminidase and hemagglutinin
2) We demonstrated that mixed rSAMs featuring ligand-terminated groups form adaptable surfaces that are optimal for multivalent receptor binding
3) The selected rSAMs were transferred on the 3D surfaces such as gold nanoparticles, nanorods, and nanosquares
4) We have demonstrated that the resulted 3D multivalent hybrid materials bind the viral proteins and can be used as for antibody-free ultrasensitive and robust sensors for rapid in situ detection of viruses and virus inhibition.
Overall, the project has produced commercially exploitable results. We have engaged in a proof-of-concept study with leading sensor companies and the ER is currently acting as principal investigator in an industry-academia collaborative project. Finally, the technology developed by the ER has been patented and will be disseminated in a number of publications in preparation.
