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Understanding how cells function requires tools that can record their molecular interactions as they occur. Scientists at the University of Michigan have developed a new technology that allows just that—a biological “tape recorder” capable of monitoring and archiving the activities of living cells across large populations and over extended periods.
Developed in the lab of Changyang Linghu, the system—called CytoTape—is a flexible, intracellular protein fiber engineered with the help of artificial intelligence. Its design enables cells to capture their own activity patterns over time by embedding recordable molecular signals along a growing protein thread. The study describing this innovation was published in Nature.
Conventional imaging techniques face limits: functional MRI provides broad views of brain activity but lacks cellular detail, while light microscopy captures single cells but cannot track live changes through dense tissue. CytoTape addresses this challenge by logging molecular activity inside living cells, leaving a timestamped record that can later be examined using standard microscopy methods.
“Just like tree rings, which encode physiological histories of a growing tree, CytoTape records temporal cell activities in situ along a flexible intracellular protein fiber for post-mortem readout at scale under conventional light microscopy, breaking through the tradeoff between resolution and scale,” said Linghu.
To create this recording system, the research team used established gene delivery methods to introduce DNA encoding the tape’s building blocks into cells. “We found CytoTape does not alter normal cell physiology or mouse brain function in vivo,” said co-lead author Lirong Zheng. Once inside the cell, these components self-assemble and elongate over time, incorporating color-coded molecular tags that mark different cellular activities.
“The presence of these tagged tape monomers are controlled by individual cell activity-dependent promoters, to leave an imprint on this tape when there is a corresponding kind of cell activity,” said co-lead author Dongqing Shi. Using this method, the team recorded transcriptional activity from over 14,000 neurons in a mouse brain.
Applying CytoTape to both mouse and human-derived cells, the researchers observed new patterns of regulatory dynamics related to cell plasticity. As Linghu noted, “By comparing the results between healthy and diseases brains, we may be able to pinpoint what goes wrong exactly across space and time in these processes and provide insights into future therapeutic interventions to correct these differences.”
Publication details: Zheng, L., Shi, D., Yan, Y. et al. Scalable and multiplexed recorders of gene regulation dynamics across weeks. Nature (2026). https://doi.org/10.1038/s41586-026-10156-9
Developed in the lab of Changyang Linghu, the system—called CytoTape—is a flexible, intracellular protein fiber engineered with the help of artificial intelligence. Its design enables cells to capture their own activity patterns over time by embedding recordable molecular signals along a growing protein thread. The study describing this innovation was published in Nature.
Conventional imaging techniques face limits: functional MRI provides broad views of brain activity but lacks cellular detail, while light microscopy captures single cells but cannot track live changes through dense tissue. CytoTape addresses this challenge by logging molecular activity inside living cells, leaving a timestamped record that can later be examined using standard microscopy methods.
“Just like tree rings, which encode physiological histories of a growing tree, CytoTape records temporal cell activities in situ along a flexible intracellular protein fiber for post-mortem readout at scale under conventional light microscopy, breaking through the tradeoff between resolution and scale,” said Linghu.
To create this recording system, the research team used established gene delivery methods to introduce DNA encoding the tape’s building blocks into cells. “We found CytoTape does not alter normal cell physiology or mouse brain function in vivo,” said co-lead author Lirong Zheng. Once inside the cell, these components self-assemble and elongate over time, incorporating color-coded molecular tags that mark different cellular activities.
“The presence of these tagged tape monomers are controlled by individual cell activity-dependent promoters, to leave an imprint on this tape when there is a corresponding kind of cell activity,” said co-lead author Dongqing Shi. Using this method, the team recorded transcriptional activity from over 14,000 neurons in a mouse brain.
Applying CytoTape to both mouse and human-derived cells, the researchers observed new patterns of regulatory dynamics related to cell plasticity. As Linghu noted, “By comparing the results between healthy and diseases brains, we may be able to pinpoint what goes wrong exactly across space and time in these processes and provide insights into future therapeutic interventions to correct these differences.”
Publication details: Zheng, L., Shi, D., Yan, Y. et al. Scalable and multiplexed recorders of gene regulation dynamics across weeks. Nature (2026). https://doi.org/10.1038/s41586-026-10156-9