Citation: Haozhi Lei, Qian Xia, Xiqiu Wang, Yang Sun, Weihong Tan. Simulation of immune signal transduction through DNA strand displacement[J]. Chinese Chemical Letters, ;2025, 36(12): 110941. doi: 10.1016/j.cclet.2025.110941 shu

Simulation of immune signal transduction through DNA strand displacement

Haozhi Lei ^{a, *,} ,
Qian Xia ^a ,
Xiqiu Wang ^a ,
Yang Sun ^{a, c, *,} ,
Weihong Tan ^{a, b, *,}

a.
Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
b.
The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China
c.
Molecular Science and Biomedicine Laboratory (MBL), National Key Laboratory of Chemo/Biosensing, College of Chemistry and Chemical Engineering, College of Biology, Hunan University, Changsha 410082, China

kflhz@mail.ustc.edu.cn

suny1989@sjtu.edu.cn

tan@hnu.edu.cn

Received Date: 4 November 2024
Revised Date: 7 February 2025
Accepted Date: 10 February 2025
Available Online: 12 February 2025

Figures(4)

Upon encountering external challenges, immune cell recognition of response to pathogens constitutes a pivotal physiological process. Here, we designed and engineering an artificial immune signal transduction system utilizing DNA strands and liposomes to simulate antigen signals presentation, i.e., the uptake and processing of antigens by antigen-presenting cells (APCs). Through controlled DNA strand displacement reactions, we engineered artificial antigen-presenting cells (mAPCs) that display antigen signals on their surface and mimic phagocytosis. To further simulate antigen presentation, we constructed mimic naïve T cells (mTCs). Then, deoxyribonucleic acid (DNA) ion channels across mTCs membranes, simulating T-cell receptors, were opened by DNA strands on mAPCs mimicking the major histocompatibility complex (MHC), i.e., MHC molecules that present peptides to the T-cell receptor (TCR) on mTCs (recognition). This allowed Ca²⁺ ions to enter mTCs, increasing calcein fluorescence as activated mTC response indicator. The DNA strands on the surface of A-mAPCs and the Ca²⁺ ions in the solution together act like costimulatory molecules on APCs to trigger responses of mTCs. This simulation of immune signal transduction provides a significant reference value for the construction of bioinspired signal transduction systems and the design of more realistic artificial biological systems.
- DNA strand displacement,
- Liposomes,
- Bioinspiration,
- Signal transduction,
- Artificial immune response
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