TY - JOUR
T1 - Programmable DNA-augmented hydrogels for controlled activation of human lymphocytes
AU - Zhovmer, Alexander S.
AU - Chandler, Morgan
AU - Manning, Alexis
AU - Afonin, Kirill A.
AU - Tabdanov, Erdem D.
N1 - Funding Information:
Financial support information: A.S.Z. was supported by the FDA Intramural Research and NHLBI Division of Intramural Research (HL006209). Also, research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Numbers R01GM120487 and R35GM139587 (to K.A.A). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. E.D.T. is supported by the Department of Pharmacology startup funds from Penn State College of Medicine. All authors declare no financial conflict of interest associated with this study.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.nano.2021.102442
DO - 10.1016/j.nano.2021.102442
M3 - Article
C2 - 34284132
AN - SCOPUS:85113212147
VL - 37
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
M1 - 102442
ER -