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Differential Effect of Simulated Microgravity on the Cellular Uptake of Small Molecules

2024; Multidisciplinary Digital Publishing Institute; Volume: 16; Issue: 9 Linguagem: Inglês

10.3390/pharmaceutics16091211

1999-4923

Odelia Tepper, Nino Tetro, Roa’a Hamed, Natalia Erenburg, Emmanuelle Merquiol, Gourab Dey, Agam Haim, Tali Dee, Noa Duvdevani, Talin Kevorkian, Galia Blum, Eylon Yavin, Sara Eyal,

3D Printing in Biomedical Research

The space environment can affect the function of all physiological systems, including the properties of cell membranes. Our goal in this study was to explore the effect of simulated microgravity (SMG) on the cellular uptake of small molecules based on reported microgravity-induced changes in membrane properties. SMG was applied to cultured cells using a random-positioning machine for up to three hours. We assessed the cellular accumulation of compounds representing substrates of uptake and efflux transporters, and of compounds not shown to be transported by membrane carriers. Exposure to SMG led to an increase of up to 60% (p < 0.01) in the cellular uptake of efflux transporter substrates, whereas a glucose transporter substrate showed a decrease of 20% (p < 0.05). The uptake of the cathepsin activity-based probe GB123 (MW, 1198 g/mol) was also enhanced (1.3-fold, p < 0.05). Cellular emission of molecules larger than ~3000 g/mol was reduced by up to 50% in SMG (p < 0.05). Our findings suggest that short-term exposure to SMG could differentially affect drug distribution across membranes. Longer exposure to microgravity, e.g., during spaceflight, may have distinct effects on the cellular uptake of small molecules.