Naked mole rat hyaluronan - an extreme folding biopolymer

Hyaluronan (HA) is a key component of the extracellular matrix of the cancer-resistant naked mole-rat (NMR). Given the fundamental role of HA in cancer, we undertook to explore the structural and soft matter properties of this ultra-high molecular weight biopolymer. We examined HA extracted from brain, lung, and skin as well as that isolated from the medium of immortalised cells. In common with mouse HA, NMR HA forms a range of assemblies corresponding to a wide distribution of molecular weights. However, unique to the NMR, are highly folded structures, whose characteristic morphology is dependent on the tissue type. Skin HA forms tightly packed assemblies that have spring like mechanical properties in addition to a strong affinity for water. Brain HA forms three dimensional folded structures similar to the macroscopic appearance of the gyri and sulci of the human brain. Lung HA forms an impenetrable mesh of interwoven folds in a morphology that can only be described as resembling a snowman. All of these readily form robust gels without the need for chemical cross-linking and sharply transition from viscoelastic to elastic like properties upon dehydration or repeated loading. Given the role of HA in maintaining hydration in the skin it is plausible that these folded structures contribute to both the elasticity and youthfullness of NMR skin. It is also possible that such densely folded structures could present a considerable barrier to cell invasion throughout the tissues.