Dynamic Behavior of RNA Nanoparticles Analyzed by AFM on a Mica/Air Interface

Sameer Sajja, Morgan Chandler, Dmitry Fedorov, Wojciech K. Kasprzak, Alexander Lushnikov, Mathias Viard, Ankit Shah, Dylan Dang, Jared Dahl, Beamlak Worku, Marina A. Dobrovolskaia, Alexey Krasnoslobodtsev, Bruce A. Shapiro, Kirill A. Afonin

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

RNA is an attractive biopolymer for engineering self-assembling materials suitable for biomedical applications. Previously, programmable hexameric RNA rings were developed for the controlled delivery of up to six different functionalities. To increase the potential for functionalization with little impact on nanoparticle topology, we introduce gaps into the double-stranded regions of the RNA rings. Molecular dynamic simulations are used to assess the dynamic behavior and the changes in the flexibility of novel designs. The changes suggested by simulations, however, cannot be clearly confirmed by the conventional techniques such as nondenaturing polyacrylamide gel electrophoresis (native-PAGE) and dynamic light scattering (DLS). Also, an in vitro analysis in primary cultures of human peripheral blood mononuclear cells does not reveal any discrepancy in the immunological recognition of new assemblies. To address these deficiencies, we introduce a computer-assisted quantification strategy. This strategy is based on an algorithmic atomic force microscopy (AFM)-resolved deformation analysis of the RNA nanoparticles studied on a mica/air interface. We validate this computational method by manual image analysis and fitting it to the simulation-predicted results. The presented nanoparticle modification strategy and subsequent AFM-based analysis are anticipated to provide a broad spectrum approach for the future development of nucleic acid-based nanotechnology.

Original languageEnglish (US)
Pages (from-to)15099-15108
Number of pages10
JournalLangmuir
Volume34
Issue number49
DOIs
StatePublished - Dec 11 2018

ASJC Scopus subject areas

  • Materials Science(all)
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Spectroscopy
  • Electrochemistry

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    Sajja, S., Chandler, M., Fedorov, D., Kasprzak, W. K., Lushnikov, A., Viard, M., Shah, A., Dang, D., Dahl, J., Worku, B., Dobrovolskaia, M. A., Krasnoslobodtsev, A., Shapiro, B. A., & Afonin, K. A. (2018). Dynamic Behavior of RNA Nanoparticles Analyzed by AFM on a Mica/Air Interface. Langmuir, 34(49), 15099-15108. https://doi.org/10.1021/acs.langmuir.8b00105