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乳酸诱导的滑液胶体微流变学。

Lactic Acid-Induced Colloidal Microrheology of Synovial Fluids.

机构信息

Department of Chemical Engineering, Indian Institute of Technology Guwahati, Assam 781039, India.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India.

出版信息

ACS Biomater Sci Eng. 2024 May 13;10(5):3378-3386. doi: 10.1021/acsbiomaterials.3c01846. Epub 2024 Mar 22.

Abstract

The presence of colloidal scaffolds composed of proteins and hyaluronic acid engenders unique viscous and elastic properties to the synovial fluid (SF). While the elastic resistance of SF due to the presence of such nanoscale structures provides the load-bearing capacity, the viscous nature enables fluidity of the joints during the movements to minimize the wear and tear of the adjacent muscle, cartilage, or bone tissues. It is well-known that the hypoxic conditions at the bone joints often increase the lactic acid (LA) concentration due to the occurrence of excess anaerobic respiration during either hyperactivity or arthritic conditions. The present study uncovers that in such a scenario, beyond a critical loading of LA, the colloidal nanoscaffolds of SF break down to precipitate higher molecular weight (MW) proteins and hyaluronic acid (HA). Subsequently, the viscosity and elasticity of SF reduce drastically to manifest a fluid that has reduced load bearing and wear and tear resistance capacity. Interestingly, the study also suggests that a heathy SF is a viscoelastic fluid with a mild Hookean elasticity and non-Newtonian fluidity, which eventually transforms into a viscous watery liquid in the presence of a higher loading of LA. We employ this knowledge to biosynthesize an artificial SF that emulates the characteristics of the real one. Remarkably, the spatiotemporal microscopic images uncover that even for the artificial SF, a dynamic cross-linking of the high MW proteins and HA takes place before precipitating out of the same from the artificial SF matrix, emulating the real one. Control experiments suggest that this phenomenon is absent in the case when LA is mixed with either pure HA or proteins. The experiments unfold the specific role of LA in the destruction of colloidal nanoscaffolds of synovia, which is an extremely important requirement for the biosynthesis and translation of artificial synovial fluid.

摘要

由蛋白质和透明质酸组成的胶体支架赋予滑液(SF)独特的粘性和弹性。虽然由于纳米级结构的存在,SF 的弹性阻力提供了承载能力,但粘性使关节在运动时具有流动性,以最大程度地减少相邻肌肉、软骨或骨组织的磨损。众所周知,由于在过度活跃或关节炎情况下发生过多的无氧呼吸,骨关节的缺氧条件通常会增加乳酸(LA)的浓度。本研究揭示,在这种情况下,超过 LA 的临界负载,SF 的胶体纳米支架会分解,沉淀出更高分子量(MW)的蛋白质和透明质酸(HA)。随后,SF 的粘度和弹性会急剧降低,表现出一种具有较低承载能力和抗磨损能力的流体。有趣的是,该研究还表明,健康的 SF 是一种具有轻微胡克弹性和非牛顿流变性的粘弹性流体,最终在 LA 负载较高的情况下会变成粘性水样液体。我们利用这一知识来生物合成一种人工 SF,模拟真实 SF 的特性。值得注意的是,时空微观图像揭示,即使对于人工 SF,在从人工 SF 基质中沉淀出高 MW 蛋白质和 HA 之前,也会发生高 MW 蛋白质和 HA 的动态交联,模拟真实 SF。对照实验表明,当 LA 与纯 HA 或蛋白质混合时,这种现象不存在。该实验揭示了 LA 在破坏滑膜胶体纳米支架中的特殊作用,这是人工合成滑液生物合成和转化的极其重要的要求。

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