Closing the Loop Between Synthetic and Living Cells
- 1Department of Chemistry
- 2Imperial College London
Abstract
Synthetic cells are moving beyond compartmentalised microreactors to become integrated components of biological networks that physically and chemically merge with their hosts. Existing reviews classify this field by mode of emission, by chemistry, or by architecture, and so describe the construct rather than its effect. This review takes the receiver's side, treating the functional adaptation of the living host as the readout of bio-hybrid function: how living cells probe their synthetic partners mechanically and adapt to them metabolically. We consider the bio-hybrid interface by how far the feedback loop (sensing-actuation) is closed and set out the evidence that would place a study in each of four tiers: open-loop, half-loop, partial feedback, and closed-loop. Read against these criteria, fifteen of the eighteen studies surveyed here are half-loop, three reach partial feedback, and none is closed-loop. All three partial-feedback systems work the same way, by metabolic interception, which the existing taxonomies have no category for. The one construct that comes closest to closed-loop operation contains no living cell at all. We then trace how single-cell coupling is scaling into hybrid prototissues that act as discovery platforms for pathological microenvironments, and we outline the translational barriers these constructs must survive to reach the clinic.
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BibTeX
@misc{ioannou2026closing,
title = {{Closing the Loop Between Synthetic and Living Cells}},
author = {Ion Ioannou},
howpublished = {ChemRxiv},
year = {2026},
month = sep,
doi = {10.26434/chemrxiv.15009350/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009350/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Closing the Loop Between Synthetic and Living Cells
AU - Ion Ioannou
PY - 2026
DA - 2026/09/23
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009350/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009350/v1
AB - Synthetic cells are moving beyond compartmentalised microreactors to become integrated components of biological networks that physically and chemically merge with their hosts. Existing reviews classify this field by mode of emission, by chemistry, or by architecture, and so describe the construct rather than its effect. This review takes the receiver's side, treating the functional adaptation of the living host as the readout of bio-hybrid function: how living cells probe their synthetic partners mechanically and adapt to them metabolically. We consider the bio-hybrid interface by how far the feedback loop (sensing-actuation) is closed and set out the evidence that would place a study in each of four tiers: open-loop, half-loop, partial feedback, and closed-loop. Read against these criteria, fifteen of the eighteen studies surveyed here are half-loop, three reach partial feedback, and none is closed-loop. All three partial-feedback systems work the same way, by metabolic interception, which the existing taxonomies have no category for. The one construct that comes closest to closed-loop operation contains no living cell at all. We then trace how single-cell coupling is scaling into hybrid prototissues that act as discovery platforms for pathological microenvironments, and we outline the translational barriers these constructs must survive to reach the clinic.
ER -