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Spatially Reprogramed Receptor Organization to Switch Cell Behavior Using a DNA Origami-Templated Aptamer Nanoarray.

Miao Wang1, Donglei Yang2, Qin Lu3

  • 1State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha, Hunan 410082, P. R. China.

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We developed a DNA nanoplatform to precisely control receptor tyrosine kinase (RTK) oligomerization, enabling new insights into cell signaling. This tool offers robust control over cellular behaviors by regulating RTK activation.

Keywords:
Aptamer ligandCellular behaviorDNA origamiMultivalencyReceptor oligomerization

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Area of Science:

  • Molecular Biology
  • Nanotechnology
  • Cell Signaling

Background:

  • Receptor oligomerization is crucial for cell signaling but lacks precise molecular interrogation tools.
  • Understanding how receptor oligomerization governs signaling responses is a significant challenge.

Purpose of the Study:

  • To develop a novel DNA origami-templated aptamer nanoarray (DOTA) for precise control over receptor tyrosine kinase (RTK) oligomerization.
  • To investigate the impact of defined valency, distribution, and stoichiometry on RTK signaling.
  • To demonstrate the utility of DOTA in regulating cellular behaviors.

Main Methods:

  • Fabrication of DNA origami-templated aptamer nanoarrays (DOTA).
  • Programming RTK oligomerization using monomeric (mALs) and dimeric (dALs) aptamer ligands.
  • Assessing RTK signaling activation and cellular response (epithelial-to-mesenchymal transition).

Main Results:

  • DOTA precisely controls RTK oligomerization with defined valency, distribution, and stoichiometry.
  • Multivalency and nanoscale spacing of RTK oligomers significantly influence signaling activation.
  • DOTA-modulated RTK oligomerization can switch cell behavior, promoting epithelial-to-mesenchymal transition.

Conclusions:

  • DOTA is a versatile DNA nanoplatform for systematic investigation and regulation of receptor-mediated cellular responses.
  • Precise control over RTK oligomerization offers a powerful method to study and manipulate cell signaling.
  • This technology opens new avenues for understanding and controlling complex cellular processes.