![]() Tardigrades are microscopic, eight-legged, animals phylogenetically related to arthropods and nematodes 4. One such anhydrobiotic organism is the tardigrade, known colloquially as a water bear 4. Once in this anhydrobiotic state, dried organisms can persist for weeks, years, and in extreme cases centuries, and reactivate metabolism and resume life processes upon rehydration 1, 2, 3. For this to occur, these specialized organisms enter a state of suspended animation known as anhydrobiosis (Greek for ‘life without water’) 1, 2, 3. However, a number of organisms across all biological kingdoms challenge this assertion by losing all, or nearly all, of the bulk water inside their bodies and cells and yet somehow surviving. Water is required for all metabolic processes and is therefore often considered essential for life. Beyond desiccation tolerance, our study provides insights into how the solution environment tunes intrinsically disordered proteins’ functions, many of which are vital in biological contexts such as development and disease that are concomitant with large changes in intracellular chemistry. This demonstrates that trehalose acts not only as a protectant, but also as a synergistic cosolute. In vivo, this synergistic interaction is required for robust CAHS-mediated protection. In vitro, naturally occurring stoichiometries of trehalose and CAHS proteins, intrinsically disordered proteins with known protective capabilities, were found to produce synergistic protective effects during desiccation. Using comparative metabolomics, we find that despite being enriched at low levels, trehalose is a key biomarker distinguishing hydration states of tardigrades. Unlike many desiccation-tolerant organisms that accumulate high levels of the disaccharide trehalose to protect themselves during drying, tardigrades accumulate little or undetectable levels. ![]() Tardigrades are microscopic animals renowned for their ability to survive extreme desiccation. ![]()
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