The deep-sea hosts ~70% of the global biosphere with rich biodiversity under pressure up to 100 MPa. Understanding how pressure-loving organisms (piezophiles) cope with the detrimental effects of high pressure offers crucial insight into the evolution of life in extreme environments. Physiological conditions like the high-pressure neurological syndrome (HPNS) post significant hindrance for human exploration of the deep sea.. While many studies have been carried at cellular level, the molecular mechanisms of piezophilicity and deep-sea physiology is still unclear. I discuss our efforts in tackling these questions with a physical chemistry approach. We study the effect of high hydrostatic pressure (HHP) on cell membranes using phospholipid bilayers (PBs) as model systems, map the biologically relevant pressure-temperature (P-T) phase space of PBs by in situ Raman spectroscopy, and identify the conformational changes associated with each phase boundary by MD simulations. We demonstrate unsaturated phospholipids hinder the formation of ordered phases, thereby retaining membrane fluidity and cell vitality under HHP. We use this platform to study the molecular origin of HPNS, i.e., overexcitability of the central neural system in the presence of high-pressure helium. Helium significantly destabilizes the crystalline phase of PBs, leading to the postulation that HPNS is caused by disruption of the lipid rafts where neurotransmitter acceptors reside. These results provide an atomistic insight into the deep-sea adaptivity of piezophiles, and guiding strategies for human exploration of previously off-limit environments.

Probing the molecular foundation of deep-sea adaptation and physiology by in situ spectroscopy and simulation

ACS Spring 2022

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