Exposing living tissue to subfreezing temperatures for long can cause irreparable damage. Microscopic ice crystals shred cells and seize moisture, making donor organs unsuitable for transplantation. Thus, organs can be chilled for only a few hours ahead of a procedure. But a set of durable new antifreeze compounds—similar to those found in particularly hardy animals—could lengthen organs’ shelf life.
Scientists at the University of Warwick in England were inspired by proteins in some species of Arctic fish, wood frogs and other organisms that prevent blood from freezing, allowing them to flourish in extreme cold. Previous research had shown these natural antifreeze molecules could preserve rat hearts at −1.3 degrees Celsius for up to 24 hours. But these proteins are expensive to extract and highly toxic to some species. “For a long time everyone assumed you had to make synthetic alternatives that looked exactly like antifreeze proteins to solve this problem,” says Matthew Gibson, a chemist at Warwick who co-authored the new research. “But we found that you can design new molecules that function like antifreeze proteins but do not necessarily look like them.”
Most natural antifreeze molecules have a patchwork of regions that either attract or repel water. Scientists do not know exactly how this process stymies ice crystal formation, but Gibson thinks it might throw water molecules into push-pull chaos that prevents them from clumping into ice. To replicate this mechanism, he and his colleagues synthesized spiral-shaped molecules that were mostly water-repellent—but had iron atoms at their centers that made them hydrophilic, or water-loving. The resulting compounds, described in July in the Journal of the American Chemical Society, were surprisingly potent at stopping ice crystals from forming. Some were also nontoxic to the roundworm Caenorhabditis elegans, indicating they might be safe for other animals.
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“These mimics are really cool because they are not proteins—they are other types of molecules that nonetheless can do at least part of what natural antifreeze proteins do,” says Clara do Amaral, a biologist at Mount St. Joseph University, who was not involved in the research. Gibson's antifreeze compounds will still need to be tested in humans, however, and may be only part of a solution. “We don't have the whole picture yet,” do Amaral adds. “It's not just one magical compound that helps freeze-tolerant organisms survive. It's a whole suite of adaptations.”