DNA probes that store mechanical information reveal transient piconewton forces applied by T cells

Proceedings of the National Academy of Sciences of the United States of America
Rong MaKhalid Salaita

Abstract

The advent of molecular tension probes for real-time mapping of piconewton forces in living systems has had a major impact on mechanobiology. For example, DNA-based tension probes have revealed roles for mechanics in platelet, B cell, T cell, and fibroblast function. Nonetheless, imaging short-lived forces transmitted by low-abundance receptors remains a challenge. This is a particular problem for mechanoimmunology where ligand-receptor bindings are short lived, and a few antigens are sufficient for cell triggering. Herein, we present a mechanoselection strategy that uses locking oligonucleotides to preferentially and irreversibly bind DNA probes that are mechanically strained over probes at rest. Thus, infrequent and short-lived mechanical events are tagged. This strategy allows for integration and storage of mechanical information into a map of molecular tension history. Upon addition of unlocking oligonucleotides that drive toehold-mediated strand displacement, the probes reset to the real-time state, thereby erasing stored mechanical information. As a proof of concept, we applied this strategy to study OT-1 T cells, revealing that the T cell receptor (TCR) mechanically samples antigens carrying single amino acid mutations. ...Continue Reading

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Citations

Jan 25, 2020·The Journal of Cell Biology·Daniel Blumenthal, Janis K Burkhardt
Sep 14, 2019·Science·Aaron T Blanchard, Khalid Salaita
Oct 19, 2019·Nature Methods·Vivien Marx
Jun 9, 2020·Frontiers in Immunology·Nayan D Bhattacharyya, Carl G Feng
Jun 6, 2020·Journal of Cell Science·Francesco BaschieriGuillaume Montagnac
Apr 11, 2020·Biology of the Cell·Mélanie ChabaudClaire Hivroz
Nov 6, 2020·Nucleic Acids Research·Wei-Hung JungYun Chen
Dec 8, 2020·Frontiers in Bioengineering and Biotechnology·Badri Narayanan NarasimhanJenny Malmström
Dec 22, 2020·Advanced Science·Rui LiWeiqiang Chen
Feb 27, 2021·Biosensors & Bioelectronics·Xinxin HangLingqian Chang
Dec 15, 2020·Physical Biology·Aaron T Blanchard, Khalid Salaita
Mar 17, 2021·Trends in Biotechnology·Andreas SchoenitKerstin Göpfrich
Jul 10, 2021·Angewandte Chemie·Yuxin DuanKhalid Salaita
Nov 5, 2020·Journal of Chemical Theory and Computation·Megan C EngelJonathan P K Doye
Dec 2, 2020·Accounts of Chemical Research·Kewen LeiLi Tang
Aug 20, 2021·Science Advances·Adam B Yasunaga, Isaac T S Li
Jun 13, 2020·ACS Chemical Biology·Ashley K Nguyen, Kristopher A Kilian
Jul 25, 2020·The Journal of Physical Chemistry. B·Paul D CunninghamJoseph S Melinger
Jan 9, 2021·ACS Applied Materials & Interfaces·Roxanne GlazierKhalid Salaita
Sep 9, 2021·Biomaterials Science·Qunye HeZhenbao Liu
Sep 17, 2021·Proceedings of the National Academy of Sciences of the United States of America·Kevin Y ChenSimon J Davis
Jul 3, 2021·Annual Review of Cell and Developmental Biology·Baoyu LiuBrian D Evavold

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