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Strategies for monitoring cell–cell interactions


Multicellular organisms depend on physical cell–cell interactions to control physiological processes such as tissue formation, neurotransmission and immune response. These intercellular binding events can be both highly dynamic in their duration and complex in their composition, involving the participation of many different surface and intracellular biomolecules. Untangling the intricacy of these interactions and the signaling pathways they modulate has greatly improved insight into the biological processes that ensue upon cell–cell engagement and has led to the development of protein- and cell-based therapeutics. The importance of monitoring physical cell–cell interactions has inspired the development of several emerging approaches that effectively interrogate cell–cell interfaces with molecular-level detail. Specifically, the merging of chemistry- and biology-based technologies to deconstruct the complexity of cell–cell interactions has provided new avenues for understanding cell–cell interaction biology and opened opportunities for therapeutic development.

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Fig. 1: Emerging technologies for investigating cell–cell interactions.
Fig. 2: Fluorescent microscopy-based methods for visualizing cell–cell interactions.
Fig. 3: Contact-dependent chemical tagging techniques for profiling cell–cell interfaces.
Fig. 4: Contact-independent chemical tagging techniques for profiling interactions at cell–cell interfaces.
Fig. 5: Functional exploitation of cell–cell interactions via cell engineering.
Fig. 6: Immunotherapies leveraging cell–cell interactions.


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We thank Y. Zheng of Yizheng Illustrations for figure design work.

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Correspondence to Olugbeminiyi O. Fadeyi or Rob C. Oslund.

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T.J.B., T.R.R., O.O.F. and R.C.O. are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

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Peer review information Nature Chemical Biology thanks Cheng Zhu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Bechtel, T.J., Reyes-Robles, T., Fadeyi, O.O. et al. Strategies for monitoring cell–cell interactions. Nat Chem Biol 17, 641–652 (2021).

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