Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Poster Session I

2 – POS Board 2 Hyaluronan Crosslinking in Synovial Fluid as Controlled by Comprehensive Biopolymer Elastic Diffusion Piotr Beldowski 1 , Adam Gadomski 1 , Satnislaw Jung 3 , Wayne Augé 2 . 1 University of Technology and Life Sciences, Bydgoszcz, Poland, 2 University of Massachusetts Dartmouth, Fall River, MA, USA, 3 University of Technology and Life Sciences, Bydgoszcz, Poland. Hyaluronic acid (HA) is one of the most ubiquitous biopolymers in the human body, displaying many biologic functions reflective of its wide-ranging molecular weight. Due to its anomalous viscoelastic and network formation properties, HA is considered an important synovial fluid (SF) component and has been implicated in both joint organ inflammatory modulation and lubrication functions at articular cartilage surfaces. Despite varied clinical success, intra-articular HA injections have been an osteoarthritis viscosupplement since the 1970s, with therapeutic efficacy being related to preparation features such as molecular weight, concentration, and dosing schedule. The aim of this work is to establish what manner HA crosslinking affects SF properties in order to optimize the viscoelastic aspects of HA supplementation deemed important for OA treatment. Because molecular weight influences the viscoelastic properties of SF as governed by the Mark-Houwink-Sakurada law, we describe three viscosity regimes undergoing Rouse and/or Zimm biopolymer chain dynamics to evaluate the ideal molecular weight range that optimizes HA crosslinking and network formation. The results indicate that a molecular weight range between 0.1 and 1 MDa equates to the most suitable viscosity regime for viscosupplementation. This viscosity regime formally displays Zimm chain dynamics in Θ solvent conditions such that when the HA biopolymer is sufficiently coiled, it is prone to form a viscoelastic network. The intrinsic network formation mechanism appears based upon the longitudinal diffusion coefficient being twice the transversal counterpart resulting in the same network spring constant ratios with an appreciable HA molecular length dependent on the rotational diffusion coefficient. These results begin to describe biopolymer molecular weight influences on the biological functions of SF hyaluronan necessary for both joint organ inflammatory modulation and lubrication functions at articular cartilage surfaces.

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