Kinetics of Molecular Recognition Mediated Nanoparticle Self-Assembly

Directed self-assembly of nanostructures into microstructures through intermolecular interactions is an important phenomenon in many biological systems. Assembly of virus coat proteins into capsids [1], of microtubulin into microtubules [2], and of collagen [3] and fi brinogen into their respective fi brils are just a few examples where self-assembly plays a critical role in biological processes. Programmed self-assembly using biomolecular interactions as a route to synthesis of novel nanostructured materials ABSTRACT Nanoscale quantum dot-antibody conjugates have been shown to self-assemble to form micron-scale aggregates in the presence of specifi c proteomic antigen. The self-assembly process exhibits sigmoidal kinetics, suggesting that nucleation limits aggregation. Self-assembly kinetics in this study is characterized by flow cytometric analysis of the aggregation reaction over time. A range of physiologically relevant concentrations of the protein angiopoietin-2, a candidate cancer biomarker, are incubated with quantum dots conjugated with a polyclonal mixture of anti-angiopoietin-2 antibodies. Antigen concentration modulates the slopes and infl ection times of the sigmoidal kinetics curves. An understanding of self-assembly kinetics in this system may lead to improvements in sensitivity and specifi city of this novel proteomic biomarker detection technique and improve the screening, diagnostics, and therapy response monitoring for cancers and other diseases. This approach to studying the kinetics of nanoparticle self-assembly may also provide a valuable tool for understanding the fundamental characteristics of nanoscale particle aggregation.