Programmable DNA-augmented hydrogels for controlled activation of human lymphocytes

Alexander S. Zhovmer, Morgan Chandler, Alexis Manning, Kirill A. Afonin, Erdem D. Tabdanov

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Contractile forces within the planar interface between T cell and antigen-presenting surface mechanically stimulate T cell receptors (TCR) in the mature immune synapses. However, the origin of mechanical stimulation during the initial, i.e., presynaptic, microvilli-based TCR activation in the course of immune surveillance remains unknown and new tools to help address this problem are needed. In this work, we develop nucleic acid nanoassembly (NAN)-based technology for functionalization of hydrogels using isothermal toehold-mediated reassociation of RNA/DNA heteroduplexes. Resulting platform allows for regulation with NAN linkers of 3D force momentum along the TCR mechanical axis, whereas hydrogels contribute to modulation of 2D shear modulus. By utilizing different lengths of NAN linkers conjugated to polyacrylamide gels of different shear moduli, we demonstrate an efficient capture of human T lymphocytes and tunable activation of TCR, as confirmed by T-cell spreading and pY foci.

Original languageEnglish (US)
Article number102442
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume37
DOIs
StatePublished - Oct 2021

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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