Abstract
Hyaluronan (HA) is a key component of the extracellular matrix. Given the fundamental role of HA in the cancer resistance of the naked mole-rat (NMR), we undertook to explore the structural and soft matter properties of this species-specific variant, a necessary step for its development as a biomaterial. We examined HA extracted from NMR 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. Unlike HA that is commercially available, NMR HA readily forms robust gels without the need for chemical cross-linking. NMR HA gels sharply transition from viscoelastic to elastic like properties upon dehydration or repeated loading. In addition, NMR HA can form ordered thin films with an underlying semi-crystalline structure. Given the role of HA in maintaining hydration in the skin it is plausible that the folded structures contribute to both the elasticity and youthfulness of NMR skin. It is also possible that such densely folded materials could present a considerable barrier to cell invasion throughout the tissues, a useful characteristic for a biomaterial.
Highlights
The naked mole-rat (NMR, Heterocephalus glaber) has a remarkable biology
The first tissue examined was skin as the characteristic wrinkly, yet stretchy skin of the NMR has been speculatively attributed to the presence of a high molecular weight HA18
Using a biotinylated version of the very specific and tightly binding hyaluronan binding protein (HABP)[28], histological analysis of the plantar surface, forepaw skin demonstrated that HA was present in both mouse and NMR skin
Summary
The naked mole-rat (NMR, Heterocephalus glaber) has a remarkable biology. They can live for up to ten times longer than sized rodents and rarely develop cancer[15,16,17]. The authors reported that it was possible the ultrahigh molecular weight (greater than 6,100 kDa) form of HA found in the NMR contributed to the elasticity of its characteristic wrinkly skin. With such unusual functions attributed to NMR HA it raises the question of if there is anything in its structure or soft matter properties that could explain its functionality?. (AFM) in air (as opposed to in aqueous solution) to interrogate the morphology of molecular scale nanostructures Both loose coils of individual molecular chains and extended structures were observed to assemble, with characteristic planar branched network structures common[19,21,23,24]. The aim of this work was to purify NMR-HA and examine the material and structural properties with particular emphasis on differences and similarities between HA from other species
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