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

Author:

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

Abstract

AbstractAquaporin-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.

Funder

Connie Frank Fellowship

University of California, Santa Barbara

Cancer Research Coordinating Committee

National Institutes of Health

Searle Scholars Program

Institute for Collaborative Biotechnologies

Brain and Behavior Research Foundation

Publisher

Springer Science and Business Media LLC

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