Closed-loop optogenetic control of cell biology enables outcome-driven microscopy

Josiah B Passmore; Alfredo Rates; Jakob Schröder; Menno T P van Laarhoven; Vincent J W Hellebrekers; Henrik G van Hoef; Antonius J M Geurts; Wendy van Straaten; Wilco Nijenhuis; Florian Berger; Carlas S Smith; Ihor Smal; Lukas C Kapitein

doi:10.1038/s41467-025-67848-5

Closed-loop optogenetic control of cell biology enables outcome-driven microscopy

Josiah B Passmore
, Alfredo Rates
, Jakob Schröder
, Menno T P van Laarhoven
, Vincent J W Hellebrekers
, Henrik G van Hoef
, Antonius J M Geurts
, Wendy van Straaten
, Wilco Nijenhuis
, Florian Berger
, Carlas S Smith
, Ihor Smal
, Lukas C Kapitein

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Smart microscopy is transforming biological imaging by integrating real-time analysis with adaptive acquisition to enhance imaging efficiency. Whereas many emerging implementations are event-driven and focus on on-demand data acquisition to reduce phototoxicity, we here present 'outcome-driven' microscopy, a framework combining smart microscopy with optogenetics to control cell biological processes and achieve predefined outcomes. We validate this approach using light-based control of cell migration and nucleocytoplasmic transport, demonstrating robust spatiotemporal control of cellular behaviour in single cells and in cell populations.

Original language	English
Article number	1087
Journal	Nature Communications
Volume	17
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-67848-5
Publication status	Published - 23 Dec 2025

Bibliographical note

Keywords

Optogenetics/methods
Humans
Cell Movement
Microscopy/methods
Single-Cell Analysis/methods
Animals
Microscopy, Fluorescence/methods
Light
HeLa Cells
Cell Nucleus/metabolism

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Passmore, J. B., Rates, A., Schröder, J., van Laarhoven, M. T. P., Hellebrekers, V. J. W., van Hoef, H. G., Geurts, A. J. M., van Straaten, W., Nijenhuis, W., Berger, F., Smith, C. S., Smal, I., & Kapitein, L. C. (2025). Closed-loop optogenetic control of cell biology enables outcome-driven microscopy. Nature Communications, 17(1), Article 1087. https://doi.org/10.1038/s41467-025-67848-5

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AU - Rates, Alfredo

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AU - Hellebrekers, Vincent J W

AU - van Hoef, Henrik G

AU - Geurts, Antonius J M

AU - van Straaten, Wendy

AU - Nijenhuis, Wilco

AU - Berger, Florian

AU - Smith, Carlas S

AU - Smal, Ihor

AU - Kapitein, Lukas C

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KW - Optogenetics/methods

KW - Humans

KW - Cell Movement

KW - Microscopy/methods

KW - Single-Cell Analysis/methods

KW - Animals

KW - Microscopy, Fluorescence/methods

KW - Light

KW - HeLa Cells

KW - Cell Nucleus/metabolism

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Closed-loop optogenetic control of cell biology enables outcome-driven microscopy

Abstract

Bibliographical note

Keywords

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