Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.
School of Engineering, Newcastle University, Merz Court, Newcastle upon Tyne, NE1 7RU, UK.
Sci Rep. 2019 Apr 29;9(1):6632. doi: 10.1038/s41598-019-43194-7.
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.
透明质酸(HA)是细胞外基质的主要成分。鉴于 HA 在裸鼹鼠(NMR)的抗癌能力中起着基础性作用,我们着手探索这种物种特异性变体的结构和软物质特性,这是将其开发为生物材料的必要步骤。我们检查了从 NMR 大脑、肺和皮肤中提取的 HA,以及从永生化细胞的培养基中分离出的 HA。与鼠 HA 一样,NMR HA 形成一系列对应的组装体,分子量分布范围很广。然而,NMR 特有的是高度折叠的结构,其特征形态取决于组织类型。皮肤 HA 形成紧密堆积的组装体,除了对水有强烈的亲和力外,还具有弹簧状的机械性能。大脑 HA 形成类似于人类大脑脑回和脑沟宏观外观的三维折叠结构。肺 HA 形成一个无法穿透的交织折叠网格,其形态只能被描述为类似于雪人。与商业上可用的 HA 不同,NMR HA 无需化学交联即可轻易形成坚固的凝胶。NMR HA 凝胶在脱水或反复加载时会从粘弹性急剧转变为弹性样特性。此外,NMR HA 可以形成具有半结晶结构底层的有序薄膜。鉴于 HA 在维持皮肤水分方面的作用,折叠结构可能有助于 NMR 皮肤的弹性和年轻。也有可能这种高度折叠的材料可能会对整个组织中的细胞入侵构成相当大的障碍,这是生物材料的一个有用特性。