Life-on-hold: Lanthanoids rapidly induce a reversible ametabolic state in mammalian cells

Abstract

Until now, the ability to reversibly halt cellular processes has been limited to cryopreser-vation and several forms of anabiosis observed in living organisms. In this paper we show that incubation of living cells with a solution containing ~50 mM neodymium induces a rapid shutdown of intracellular organelle movement and all other evidence of active metabolism. We have named this state REEbernation (derived from the terms REE (rare earth elements) and hibernation) and found that the process involves a rapid replacement of calcium with neodymium in membranes and organelles of a cell, allowing it to maintain its shape and membrane integrity under extreme condi-tions, such as low pressure. Furthermore, phosphate exchange is blocked as a result of non-dissolv-able neodymium salts formation, which “discharged” the cell. We further showed that REEberna- tion is characterized by an immediate cessation of transcriptional activity in observed cells, provid-ing an intriguing opportunity to study a snapshot of gene expression at a given time point. Finally, we found that the REEbernation state is reversible, and we could restore the metabolism and proliferation capacity of the cells. The REEbernation, in addition to being an attractive model to further investigate the basic mechanisms of cell metabolism control, also provides a new method to reversibly place a cell into “on-hold” mode, opening opportunities to develop protocols for biological samples fixation with a minimum effect on the omics profile for biomedical needs.