Molecular Recognition of Ice by Fully Flexible Molecules

Abstract

Cold acclimatized organisms produce antifreeze proteins that prevent ice growth and recrystallization at subfreezing conditions. Flatness and rigidity of the ice-binding sites of antifreeze proteins are considered key for their recognition of ice. However, the most potent synthetic ice recrystallization inhibitor (IRI) found to date is poly(vinyl alcohol) (PVA), a fully flexible molecule. The ability to tune the architecture and functionalization of PVA makes it a promising candidate to replace antifreeze proteins in industrial applications ranging from cryopreservation of organs to deicing of turbine blades. However, an understanding of how does PVA recognize ice remains elusive, hampering the design of more effective IRIs. Here we use large-scale molecular simulations to elucidate the mechanism by which PVA recognizes ice. We find that the polymer selectively binds to the prismatic faces of ice through a cooperative zipper mechanism. The binding is driven by hydrogen bonding, facilitated by distance matching between the hydroxyl groups of PVA and water molecules at the ice surface. Strong, cooperative binding to ice results from the different scaling of the free energy gains on binding per monomer and the loss of translational and configurational entropy of the chain. We explain why branching of PVA does not improve its IRI activity and use the new molecular understanding to propose principles for the design of macromolecules that bind efficiently to the basal and prismatic planes of ice, producing hyperactive synthetic antifreeze molecules that could compete with the most effective antifreeze proteins.

Mimicking the Ice Recrystallization Activity of Biological Antifreezes. When is a New Polymer “Active”?

“…[33] Hyperactive AFPs, which display a larger thermal hysteresis gap can also bind the basal face. [34,35] Experimental and modeling evidence supports PVA's unique activity being due to its hydroxyls precisely matching the spacing on the prism plane of ice, and a balance of enthalpy/entropy compensation leads to increased affinity and hence inhibition [36][37][38] due to a multivalent or "zipper" effect ( Figure 2C). This also explains why many other polyols fail to inhibit growth as they do not have this extended stretch of hydroxyls with precise spacing, with a range of glycopolymers or carbohydrates (see Supporting Information) showing very little activity.…”

“…Polymer chain architecture has also shown to be important, with three‐arm PVA demonstrating IRI activity equal to that of a linear polymer the same length as two of the arms . It has been suggested that this is because of the inability of the third arm to effectively bind a basal plane of ice, as the other two arms (binding in a linear fashion) confine the third …”

“…[42] It has been suggested that this is because of the inability of the third arm to effectively bind a basal plane of ice, as the other two arms (binding in a linear fashion) confine the third. [37]…”

How Do Size and Aggregation of Ice-binding Proteins Control their Ice Nucleation Efficiency

“…The equivalent efficiency of proteins and alcohol monolayers indicates that the IBS does not need to be amphiphilic to bind strongly to ice. (3,16,32) INP width limits their ice nucleation temperature.…”

Antifreeze protein hydration waters: Unstructured unless bound to ice

“…Molinero and coworkers explore this tantalizing suggestion in a series of recent articles (5,20,21). In ref.…”