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Multicellular biological systems, most notably living neural networks, exhibit highly complex physical organization properties that pose challenges for building cell-specific and biocompatible interfaces. We developed a novel approach to genetically program cells to chemically assemble artificial structures that modify the electrical properties of neurons in situ, opening up the possibility of minimally-invasive cell-specific interfaces with neural circuits in living animals. However, the efficiency and biocompatibility of this approach were challenged by limited membrane targeting of the constructed material. Here, we report a method with significantly improved molecular construct properties, which expresses highly localized enzymes targeted to the plasma membrane of primary neurons with minimal intracellular retention. Polymers synthesized in situ by this approach form dense clusters on the targeted cell membrane, and neurons remain viable after polymerization. This platform can be readily extended to incorporate a broad range of materials onto the surface membranes of specific cells within complex tissues, using chemistry that may further enable the next generation of interfaces with living biological systems.
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Genetically-encoded photosensitizers enable light-controlled polymerization on living neuronal membranes
The ability to record, stimulate, and modify brains of living animals would unlock numerous research opportunities and create potential clinical interventions, but it is difficult to interface with a living neural network without damaging it. We previously reported a novel approach to building neural interfaces, namely: genetically programming cells to build artificial structures to modify the electrical properties of neurons in situ, which opens up the possibility of modifying neural circuits in living animals without surgery. However, the spatiotemporal resolution, efficiency, and biocompatibility of this approach were still limited and lacked selectivity on cell membrane. Here, we demonstrate an approach using genetically-targeted photosensitizers to instruct living cells to synthesize functional materials directly on the plasma membrane under the control of light. Polymers synthesized by this approach were selectively deposited on the membrane of targeted live neurons. This platform can be readily extended to incorporate a broad range of light-controlled reactions onto specific cells, which may enable researchers to grow seamless, dynamic interfaces directly in living animals.
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- Award ID(s):
- 2037164
- PAR ID:
- 10450651
- Date Published:
- Journal Name:
- bioRxiv
- ISSN:
- 2692-8205
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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