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Ice crystals represent the solid crystalline phase of water, typically forming a hexagonal lattice (Ice Ih) under physiological conditions (Gage & Baust, 1998). While not a biological macromolecule such as a protein or receptor, ice crystals are the central physical entity targeted or manipulated in cryotherapy and cryopreservation. In therapeutic cryoablation, the rapid formation of intracellular ice crystals causes lethal mechanical damage to the plasma membrane and organelles, while extracellular ice formation induces severe osmotic stress and dehydration, leading to cell death in malignant tumors or aberrant cardiac tissue (Baust et al., 2009). Conversely, in the field of cryopreservation, ice crystals are viewed as a pathological byproduct that must be inhibited; here, ice-binding proteins (IBPs) and antifreeze proteins (AFPs) act by binding to the crystal surface to prevent growth and recrystallization (Davies, 2014). Chemical cryoprotectants like dimethyl sulfoxide (DMSO) further interact with the aqueous environment to depress the freezing point and alter ice crystal kinetics to protect biological structures (Best, 2015).
Physical disruption of cellular membranes and osmotic stress leading to cell death (in cryoablation); inhibition of ice crystal growth and recrystallization (by antifreeze proteins).
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