The osmotic pressure of Chondroitin Sulfate in a simulated physiological environment of articular cartilage is thoroughly examined in silico using full atomistic models. The effects of length (4 vs. 8 monomers), sulfation type (0-, 4-, and 6-sulfation) and ionic strength were investigated in order to elucidate the molecular origins of cartilage biomechanical behavior (focusing on osmotic pressure) providing single-atomistic resolution analyses which would not be attainable with experimental techniques. CS chains exhibit plastic deformation behavior under compressive load, therefore osmotic pressure in the ECM is the main contributor balancing external pressures and this study focuses on quantitatively expressing this contribution. Molecular dynamics was used to recreate the physiological environment experienced inside the extracellular matrix of articular cartilage by CS chains and to simulate the forces acting on the full atomistic chains during compression. To this end, a variety of validation techniques, pre-simulation tasks, and comparisons were conducted in order to validate the test methodology. Preliminaries showed excellent matching results when compared with previous well established studies. Six different CS chain systems with varying lengths and sulfation positions arranged in realistic physiological environments underwent simulation under carrying molar concentrations. Sulfation positioning is found to have negligible influence on CS osmotic pressure behavior, attributed to the small distance between the position of 4- and 6- sulfation relative to the intermolecular spacing between the CS chains. However difference between sulfated and unsulfated chains did have a significant influence on the osmotic pressure. Length of chains was also found to have a significant influence on osmotic pressure as was expected. Osmotic pressures are compared to previous well-established studies and experimental data; and methods for further exploration area discussed.
La pressione osmotica di condroitin solfato (CS) in un ambiente fisiologico simulato della cartilagine articolare è accuratamente esaminata in silico utilizzando modelli atomistici completi. Gli effetti di lunghezza (4 vs 8 monomeri), tipo solfatazione (0-, 4- e 6-solfatazione) e la forza ionica sono stati studiati al fine di chiarire le origini molecolari della cartilagine comportamento biomeccanico (incentrati sulla pressione osmotica) fornendo singolo-atomistica risoluzione di analisi che non sarebbe raggiungibile con tecniche sperimentali. Catene CS mostrano un comportamento di deformazione plastica sotto carico di compressione, quindi la pressione osmotica in ECM è il principale contributore bilanciare le pressioni esterne e questo studio si concentra su quantitativamente esprimere questo contributo. Dinamica molecolare è stato utilizzato per ricreare l'ambiente fisiologico sperimentato all'interno della matrice extracellulare della cartilagine articolare da catene CS e di simulare le forze che agiscono sulle catene atomistiche completi durante la compressione. A tal fine, una varietà di tecniche di convalida, attività pre-simulazione, e confronti sono stati condotti al fine di validare la metodologia di prova. Preliminari hanno mostrato ottimi risultati corrispondenti rispetto ai precedenti studi ben consolidati. Sei diversi sistemi di catene CS con lunghezze diverse e posizioni solfatazione disposti in ambienti fisiologici realistici sottoposti a simulazione in svolgimento concentrazioni molari. Posizionamento solfatazione si trova ad avere un'influenza trascurabile sul comportamento pressione osmotica CS, attribuito alla piccola distanza tra la posizione di 4- e 6- solfatazione relative alla distanza intermolecolare tra le catene CS. Tuttavia la differenza tra le catene solfati e solforato ha avuto una notevole influenza sulla pressione osmotica. Lunghezza delle catene è stato anche scoperto di avere una notevole influenza sulla pressione osmotica, come ci si aspettava. Pressioni osmotiche sono confrontati con i precedenti studi affermati e dati sperimentali; e metodi per ulteriore zona di esplorazione discThe osmotic pressure of Chondroitin Sulfate in a simulated physiological environment of articular cartilage is thoroughly examined in silico using full atomistic models. The effects of length (4 vs. 8 monomers), sulfation type (0-, 4-, and 6-sulfation) and ionic strength were investigated in order to elucidate the molecular origins of cartilage biomechanical behavior (focusing on osmotic pressure) providing single-atomistic resolution analyses which would not be attainable with experimental techniques. CS chains exhibit plastic deformation behavior under compressive load, therefore osmotic pressure in the ECM is the main contributor balancing external pressures and this study focuses on quantitatively expressing this contribution. Molecular dynamics was used to recreate the physiological environment experienced inside the extracellular matrix of articular cartilage by CS chains and to simulate the forces acting on the full atomistic chains during compression. To this end, a variety of validation techniques, pre-simulation tasks, and comparisons were conducted in order to validate the test methodology. Preliminaries showed excellent matching results when compared with previous well established studies. Six different CS chain systems with varying lengths and sulfation positions arranged in realistic physiological environments underwent simulation under carrying molar concentrations. Sulfation positioning is found to have negligible influence on CS osmotic pressure behavior, attributed to the small distance between the position of 4- and 6- sulfation relative to the intermolecular spacing between the CS chains. However difference between sulfated and unsulfated chains did have a significant influence on the osmotic pressure. Length of chains was also found to have a significant influence on osmotic pressure as was expected. Osmotic pressures are compared to previous well-established studies and experimental data; and methods for further exploration area discussed.ussi.
Osmotic pressure characterization of glycosaminoglycans using full atomistic molecular models
PANDO, ALEJANDRO
2013/2014
Abstract
The osmotic pressure of Chondroitin Sulfate in a simulated physiological environment of articular cartilage is thoroughly examined in silico using full atomistic models. The effects of length (4 vs. 8 monomers), sulfation type (0-, 4-, and 6-sulfation) and ionic strength were investigated in order to elucidate the molecular origins of cartilage biomechanical behavior (focusing on osmotic pressure) providing single-atomistic resolution analyses which would not be attainable with experimental techniques. CS chains exhibit plastic deformation behavior under compressive load, therefore osmotic pressure in the ECM is the main contributor balancing external pressures and this study focuses on quantitatively expressing this contribution. Molecular dynamics was used to recreate the physiological environment experienced inside the extracellular matrix of articular cartilage by CS chains and to simulate the forces acting on the full atomistic chains during compression. To this end, a variety of validation techniques, pre-simulation tasks, and comparisons were conducted in order to validate the test methodology. Preliminaries showed excellent matching results when compared with previous well established studies. Six different CS chain systems with varying lengths and sulfation positions arranged in realistic physiological environments underwent simulation under carrying molar concentrations. Sulfation positioning is found to have negligible influence on CS osmotic pressure behavior, attributed to the small distance between the position of 4- and 6- sulfation relative to the intermolecular spacing between the CS chains. However difference between sulfated and unsulfated chains did have a significant influence on the osmotic pressure. Length of chains was also found to have a significant influence on osmotic pressure as was expected. Osmotic pressures are compared to previous well-established studies and experimental data; and methods for further exploration area discussed.| File | Dimensione | Formato | |
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https://hdl.handle.net/10589/94803