Crowding in Anhydrobiosis.

Anhydrobiosis, the exceptional adaptation of some organisms to enter a state approaching suspended animation after losing most cellular water, has fascinated scientists and non-scientists since Anthony van Leeuwenhoek described the phenomenon over 300 years ago. Despite progress in elucidating molecular principles enabling 'life at a standstill,' we still lack a comprehensive understanding of the minimum biochemical requirements for desiccation tolerance. Biochemical strategies employed by anhydrobiotic organisms are multifaceted but commonly include the accumulation of intrinsically disordered proteins and compatible osmolytes, investment into antioxidant defense mechanisms, and, more recently recognized, the formation of biomolecular condensates. This chapter explores why water is the solvent capable of sustaining life on Earth and how it promotes biomolecular condensates in cells. We propose four mechanisms by which these biomolecular condensates may facilitate desiccation tolerance: 1.) The selective sequestration hypothesis proposes the formation of 'protective' biomolecular condensates, 2.) The selective target neutralization hypothesis suggests that biomolecular condensates may downregulate metabolic, developmental, and apoptotic pathways during water stress, 3.) The increased viscocapillary effect hypothesis proposes that the preservation of cellular morphology can be maintained during desiccation by a combination of increased viscosity and capillary forces exerted by biomolecular condensates, and 4.) The solvent property hypothesis postulates that water's physicochemical properties inside biomolecular condensates could be modulated to inhibit damage during desiccation. Integrating the known biochemical strategies observed in anhydrobiotes into a comprehensive model of desiccation tolerance may allow us to engineer this trait into water-stress sensitive systems to address societal challenges ranging from crop loss during droughts to stabilization of biomedical relevant cells at room temperature.