Conjugation of biomolecules
on the surface of nanoparticles (NPs)
to achieve active targeting is widely investigated within the scientific
community. However, while a basic framework of the physicochemical
processes underpinning bionanoparticle recognition is now emerging,
the precise evaluation of the interactions between engineered NPs
and biological targets remains underdeveloped. Here, we show how the
adaptation of a method currently used to evaluate molecular ligand–receptor
interactions by quartz crystal microbalance (QCM) can be used to obtain
concrete insights into interactions between different NP architectures
and assemblies of receptors. Using a model bionanoparticle grafted
with oriented apolipoprotein E (ApoE) fragments, we examine key aspects
of bionanoparticle engineering for effective interactions with target
receptors. We show that the QCM technique can be used to rapidly measure
construct–receptor interactions across biologically relevant
exchange times. We contrast random adsorption of the ligand at the
surface of the NPs, resulting in no measurable interaction with target
receptors, to grafted oriented constructs, which are strongly recognized
even at lower graft densities. The effects of other basic parameters
impacting the interaction such as ligand graft density, receptor immobilization
density, and linker length were also efficiently evaluated with this
technique. Dramatic changes in interaction outcomes with subtle alterations
in these parameters highlight the general importance of measuring
the interactions between engineered NPs and target receptors ex situ
early on in the construct development process for the rational design
of bionanoparticles.