Monte Carlo simulation of freezing of confluent tissues

Summary form only given. Tissue freezing is an important phenomenon in cryopreservation and cryosurgery. Although much is known about the mechanisms and kinetics of the deleterious process of intracellular ice formation (IIF) in isolated cells, this knowledge is not sufficient to describe the formation of ice in tissues. Unlike isolated cells, cells in confluent tissues interact with each other, resulting in an increase in the probability of cell damage, due to intercellular ice propagation. In experiments in a micropatterned two-cell system, we have shown that ice propagation is mediated by gap junctions, increasing the rate of IIF by an order of magnitude. Based on these results, we have developed a theoretical model of intracellular freezing in multicellular tissues, using Monte Carlo techniques to simulate the coupled stochastic processes of ice nucleation and ice propagation. A parametric analysis is presented, demonstrating the differences in the kinetics of ice propagation between one-, two-, and three- dimensional tissue, as well as the sensitivity of the probability of IIF to variations in the number of cell neighbors and the degree of intercellular interaction. By predicting the dynamics of freezing in a tissue with a simulated tumor, conditions under which cryosurgical ablation would yield a favorable outcome were determined.