Engineering water exchange is a safe and effective method for magnetic resonance imaging in diverse cell types

Austin D C Miller; Soham P Chowdhury; Hadley W Hanson; Sarah K Linderman; Hannah I Ghasemi; Wyatt D Miller; Meghan A Morrissey; Chris D Richardson; Brooke M Gardner; Arnab Mukherjee

doi:10.1186/s13036-024-00424-5

Engineering water exchange is a safe and effective method for magnetic resonance imaging in diverse cell types

J Biol Eng. 2024 Apr 22;18(1):30. doi: 10.1186/s13036-024-00424-5.

Authors

Affiliations

¹ Biomolecular Science and Engineering Graduate Program, University of California, Santa Barbara, CA, 93106, USA.
² Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, 93106, USA.
³ Biomolecular Science and Engineering Graduate Program, University of California, Santa Barbara, CA, 93106, USA. arnabm@ucsb.edu.
⁴ Department of Chemical Engineering, University of California, Santa Barbara, CA, 93106, USA. arnabm@ucsb.edu.
⁵ Department of Bioengineering, University of California, Santa Barbara, CA, 93106, USA. arnabm@ucsb.edu.
⁶ Department of Chemistry, University of California, Santa Barbara, CA, 93106, USA. arnabm@ucsb.edu.
⁷ Neuroscience Research Institute, University of California, Santa Barbara, CA, 93106, USA. arnabm@ucsb.edu.

Abstract

Aquaporin-1 (Aqp1), a water channel, has garnered significant interest for cell-based medicine and in vivo synthetic biology due to its ability to be genetically encoded to produce magnetic resonance signals by increasing the rate of water diffusion in cells. However, concerns regarding the effects of Aqp1 overexpression and increased membrane diffusivity on cell physiology have limited its widespread use as a deep-tissue reporter. In this study, we present evidence that Aqp1 generates strong diffusion-based magnetic resonance signals without adversely affecting cell viability or morphology in diverse cell lines derived from mice and humans. Our findings indicate that Aqp1 overexpression does not induce ER stress, which is frequently associated with heterologous expression of membrane proteins. Furthermore, we observed that Aqp1 expression had no detrimental effects on native biological activities, such as phagocytosis, immune response, insulin secretion, and tumor cell migration in the analyzed cell lines. These findings should serve to alleviate any lingering safety concerns regarding the utilization of Aqp1 as a genetic reporter and should foster its broader application as a noninvasive reporter for in vivo studies.

Keywords: Cell physiology; Diffusion; MRI; Reporter gene; Unfolded protein response; aquaporin-1.

Abstract

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