Effects of Simulated Microgravity on the Internalization of Cerium Oxide Nanoparticles by Proliferating Human Skeletal Myoblasts

Spaceflight typically exerts detrimental effects on livingorganismsby promoting/accelerating some degenerative processes associated withaging and pathology onset on Earth, like muscle degeneration. As possiblecountermeasures to spaceflight effects, a few recent studies successfullytested the administration of nanomaterials for tuning of cellularactivities and for promotion of certain cell phenotypes in microgravity,but largely missed investigation of early interactions of these nanomaterialswith their cellular targets under altered gravity conditions. Thisstudy aims at filling this gap by elucidation of early interactionsof a selected typology of redox-active nanoparticles (cerium oxidenanoparticles, also termed nanoceria, NC) with proliferating humanskeletal myoblasts (HSkM) by concomitant exposure to simulated microgravity(achieved by a random positioning machine, RPM). To this purpose,NC were synthesized by a direct precipitation method and were chemically,structurally, and functionally characterized by several independenttechniques prior to administration to skeletal muscle cell culturesand loading on the RPM. Confocal and electron microscopy evidenceof nanoparticle internalization by several mechanisms (mostly involvingmacropinocytosis) in HSkM is provided, along with evidence of transcriptionalregulation of key antioxidant response markers (Nos1, Sod2, and Sod3), promising oxidativestress alleviation and muscle protection under mechanical unloadingconditions.