4.8 Article

DNA-Based Dynamic Mimicry of Membrane Proteins for Programming Adaptive Cellular Interactions

Journal

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 143, Issue 12, Pages 4585-4592

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/jacs.0c11245

Keywords

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Funding

  1. National Key Research Program [2018YFC1602900, 2019YFA0905800]
  2. National Natural Science Foundation of China [NSFC 21827811, 91753109, 21922404]
  3. Science and Technology Project of Hunan Province [2017XK2103, 2018JJ3034, 2019SK2201, 2018RS3035]
  4. China Postdoctoral Science Foundation [2020M681924, 2020TQ0269]

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A cell-surface nanoarchitecture was engineered to mimic the dynamic behavior of membrane proteins, allowing cells to respond to environmental changes. Activation by cell-responsive signals enables the assembly of multiple functional modules on the membrane for cell-type-specific binding and killing, offering a new paradigm for engineering therapeutic cells.
Cells sense and respond to the external environment, mainly through proteins presented on the membrane where their expression and conformation are dynamically regulated via intracellular programs. Here, we engineer a cell-surface nanoarchitecture that realizes molecular-recognition-initiated DNA assembly to mimic the dynamic behavior of membrane proteins, enabling the manipulation of cellular interaction in response to environmental changes. Our results show that this membrane-anchored DNA nanoarchitecture can be specifically activated by cell-responsive signals to external stimulation. Accordingly, multiple functional modules can be assembled onto the membrane to equip the cell with cell-type-specific binding and killing. This system is expected to offer a new paradigm for engineering therapeutic cells with customized sensing/response pathways.

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