The ice-water interface and protein stability: a review

The ice-water interface is commonly encountered in our life, and comes into play in a wide number of natural phenomena. Here, attention will be focused on its effects on protein stability, with specific reference to the case of pharmaceutical proteins. This field represents a fascinating, and not yet fully understood, subject of investigation. Some background information on the ice-water phase diagram, as well as to the mechanisms of nucleation and crystal growth, will be provided. We will eventually discuss the effect of ice on protein activity, reviewing the mechanisms of ice-induced denaturation that have been proposed so far and discussing the strategies that may help prevent, or minimize, undesired loss of therapeutic activity.