Photon Upconversion Hydrogels for 3D Optogenetics

Rinat Meir, Tal Hirschhorn, Sungsoo Kim, Kealan J. Fallon, Emily M. Churchill, Dino Wu, Hee Won Yang, Brent R. Stockwell, Luis M. Campos

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The ability to optically induce biological responses in 3D has been dwarfed by the physical limitations of visible light penetration to trigger photochemical processes. However, many biological systems are relatively transparent to low-energy light, which does not provide sufficient energy to induce photochemistry in 3D. To overcome this challenge, hydrogels that are capable of converting red or near-IR (NIR) light into blue light within the cell-laden 3D scaffolds are developed. The upconverted light can then excite optically active proteins in cells to trigger a photochemical response. The hydrogels operate by triplet–triplet annihilation upconversion. As proof-of-principle, it is found that the hydrogels trigger an optogenetic response by red/NIR irradiation of HeLa cells that have been engineered to express the blue-light sensitive protein Cry2olig. While it is remarkable to photoinduce the clustering of Cry2olig with blanket NIR irradiation in 3D, it is also demonstrated how the hydrogels trigger clustering within a single cell with great specificity and spatiotemporal control. In principle, these hydrogels may allow for photochemical control of cell function within 3D scaffolds, which can lead to a wealth of fundamental studies and biochemical applications.

Original languageEnglish
Article number2010907
JournalAdvanced Functional Materials
Volume31
Issue number31
DOIs
StatePublished - 2 Aug 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 Wiley-VCH GmbH

Funding

L.M.C. thanks Columbia University for funding, as well as The Cottrell Fellowship Initiative, partially funded by a National Science Foundation award to RCSA (CHE-2039044). R.M. thanks the Fulbright Program and the US–Israel Educational Foundation for funding. Confocal images were collected in the Confocal and Specialized Microscopy Shared Resource of the Herbert Irving Comprehensive Cancer Center at Columbia University, supported by NIH grant P30 CA013696 (National Cancer Institute). The confocal microscope was purchased with NIH grant S10 RR025686. H.W.Y. was supported by the Herbert Irving Comprehensive Cancer Center (P30 CA013696). B.R.S. was supported by NCI grants P01CA87497 and R35CA209896 and NINDS grant R61NS109407. B.R.S. is an inventor on patents and patent applications involving ferroptosis and small molecule therapeutics, co-founded and serves as a consultant to Inzen Therapeutics and Nevrox Limited, and serves as a consultant to Weatherwax Biotechnologies Corporation. E.M.C. thanks the NSF GRFP (1644869). D.W. thanks the Swiss National Science Foundation (SNSF). L.M.C. thanks Columbia University for funding, as well as The Cottrell Fellowship Initiative, partially funded by a National Science Foundation award to RCSA (CHE‐2039044). R.M. thanks the Fulbright Program and the US–Israel Educational Foundation for funding. Confocal images were collected in the Confocal and Specialized Microscopy Shared Resource of the Herbert Irving Comprehensive Cancer Center at Columbia University, supported by NIH grant P30 CA013696 (National Cancer Institute). The confocal microscope was purchased with NIH grant S10 RR025686. H.W.Y. was supported by the Herbert Irving Comprehensive Cancer Center (P30 CA013696). B.R.S. was supported by NCI grants P01CA87497 and R35CA209896 and NINDS grant R61NS109407. B.R.S. is an inventor on patents and patent applications involving ferroptosis and small molecule therapeutics, co‐founded and serves as a consultant to Inzen Therapeutics and Nevrox Limited, and serves as a consultant to Weatherwax Biotechnologies Corporation. E.M.C. thanks the NSF GRFP (1644869). D.W. thanks the Swiss National Science Foundation (SNSF).

FundersFunder number
Herbert Irving Comprehensive Cancer Center
US-Israel Educational Foundation
Weatherwax Biotechnologies Corporation
National Science FoundationCHE‐2039044, 1644869
National Institutes of HealthP30 CA013696
National Cancer InstituteP01CA87497, S10 RR025686, R35CA209896
National Institute of Neurological Disorders and StrokeR61NS109407
Columbia University
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

    Keywords

    • biomaterials
    • hydrogels
    • optogenetics
    • photon upconversion
    • triplet–triplet annihilation

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