Bottom-Up Synthesis of Colloidal Systems Using Sequence Defined Molecules

Abstract

Self-assembled colloidal nanoparticles can be used to deliver vaccines, sense pathogenic materials, and mark tumors. In response to light, they catalyze the formation of clean fuels or help transform it directly into usable energy.Quantum dots are used in commercial displays and will be a key step in new forms of computing and information storage. The performance of nanoparticles is dictated by their structure and composition and can be controlled using sequence defined molecules. The latter include any polymeric or oligomeric materials in which the exact sequence is precisely controlled using enzymatic processes or synthetic chemistry. Their physicochemical diversity and modularity are used to intervene in chemical processes occurring during synthesis, stabilize specific crystal facets, or form templates that guide nanomaterial growth. Yet the multivariate relationship between experimental parameters and intermolecular reactions that govern nanomaterial self-assembly is difficult to study using traditional experimental methods. In this work, gold nanoparticle synthesis in the presence of peptides is used as a model system for developing and integrating experimental automation with computational approaches to extract information for guiding sequence design.Several peptide variants were selected through systematic variations of a gold binding peptide, and nanoparticles were synthesized using a liquid handling robot in a large design space of reagent concentrations. The plasmonic response of nanoparticles was used as a fast proxy for changes in structures and was analyzed using functional data analysis methods. The analysis resulted in a metric for quantifying how changes in peptide design affect nanoparticle synthesis outcomes, and the conclusions were corroborated with small-angle X-ray scattering and electron microscopy. Next, the relationship between substitution of methionine in a peptide sequence and an increase in particle anisotropy was assessed. A programmed liquid handling robot was used to dynamically intervene in nanoparticle synthesis to control the resulting structure and stability of anisotropic nanoparticles. Finally, highlights of how small-angle X-ray scattering can work in parallel with computational methods to study colloidal self-assembly mechanisms are presented.