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DNA Mediated Assembly of Protein Heterodimers on Membrane Surfaces

  • Author(s): Coyle, Michael Patrick
  • Advisor(s): Francis, Matthew B
  • Groves, Jay T
  • et al.
Abstract

Signal transduction at cell-cell junctions is critical for many biological processes, such as the development of multicellular organisms and the recognition of damaged or infected cells. Such interfaces can be reconstituted in vitro by synthetically coupling cell surface ligands to supported membranes, which can be interfaced directly with live cells. The lateral fluidity of these membranes allows ligand receptor complexes to assemble into oligomers and higher order clusters. This type of higher order clustering has been shown to play a role in the regulation and function of various cell membrane receptors. In order to study complex, multicomponent signaling assemblies, I have extended the use of supported membranes and DNA-based protein assembly to form heterodimers of signaling molecules. Characterization of these structures was performed by fluorescence cross-correlation spectroscopy, which confirmed their lateral mobility and the formation of specific heterodimers. I have additionally demonstrated the interaction of these structures with live cells and the modulation of signaling cluster content in these cells. DNA based assembly was also used for the precise positioning of fluorophores at a fixed distance from a gold nanoparticle encased in a viral capsid. These fluorophores were protected from contact quenching, and their fluorescence was enhanced by their proximity to the gold nanoparticle. Together these studies demonstrate the use of DNA hybridization in directing the formation of functional nanoscale assemblies.

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