Application of recent advances in hydrodynamic methods for characterising mucins in solution

Mucins are the primary macromolecular component of mucus—nature’s natural lubricant—although they are poorly characterised heterogeneous substances. Recent advances in hydrodynamic methodology now offer the opportunity for gaining a better understanding of their solution properties. In this study a...

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Main Authors: Almutairi, Fahad M., Cifre, Jose-Gines Hernandez, Adams, Gary G., Kök, M. Samil, Mackie, Alan R., de la Torre, Jose Garcia, Harding, Stephen E.
Format: Article
Published: Springer 2016
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Online Access:https://eprints.nottingham.ac.uk/42720/
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author Almutairi, Fahad M.
Cifre, Jose-Gines Hernandez
Adams, Gary G.
Kök, M. Samil
Mackie, Alan R.
de la Torre, Jose Garcia
Harding, Stephen E.
author_facet Almutairi, Fahad M.
Cifre, Jose-Gines Hernandez
Adams, Gary G.
Kök, M. Samil
Mackie, Alan R.
de la Torre, Jose Garcia
Harding, Stephen E.
author_sort Almutairi, Fahad M.
building Nottingham Research Data Repository
collection Online Access
description Mucins are the primary macromolecular component of mucus—nature’s natural lubricant—although they are poorly characterised heterogeneous substances. Recent advances in hydrodynamic methodology now offer the opportunity for gaining a better understanding of their solution properties. In this study a combination of such methods was used to provide increased understanding of a preparation of porcine intestinal mucin (PIM), MUC2 mucin, in terms of both heterogeneity and quantification of conformational flexibility. The new sedimentation equilibrium algorithm SEDFIT-MSTAR is applied to yield a weight average (over the whole distribution) molar mass of 7.1 × 106 g mol−1, in complete agreement with size exclusion chromatography coupled with multi-angle light scattering (SEC-MALS), which yielded a value of 7.2 × 106 g mol−1. Sedimentation velocity profiles show mucin to be very polydisperse, with a broad molar mass distribution obtained using the Extended Fujita algorithm, consistent with the elution profiles from SEC-MALS. On-line differential pressure viscometry coupled to the SEC-MALS was used to obtain the intrinsic viscosity [η] as a function of molar mass. These data combined with sedimentation coefficient data into the global conformation algorithm HYDFIT show that PIM has a flexible linear structure, with persistence length Lp ~10 nm and mass per unit length, ML ~2380 g mol−1 nm−1, consistent with a Wales-van Holde ratio of ~1.2 obtained from the concentration dependence of the sedimentation coefficient.
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spelling nottingham-427202020-05-04T17:29:19Z https://eprints.nottingham.ac.uk/42720/ Application of recent advances in hydrodynamic methods for characterising mucins in solution Almutairi, Fahad M. Cifre, Jose-Gines Hernandez Adams, Gary G. Kök, M. Samil Mackie, Alan R. de la Torre, Jose Garcia Harding, Stephen E. Mucins are the primary macromolecular component of mucus—nature’s natural lubricant—although they are poorly characterised heterogeneous substances. Recent advances in hydrodynamic methodology now offer the opportunity for gaining a better understanding of their solution properties. In this study a combination of such methods was used to provide increased understanding of a preparation of porcine intestinal mucin (PIM), MUC2 mucin, in terms of both heterogeneity and quantification of conformational flexibility. The new sedimentation equilibrium algorithm SEDFIT-MSTAR is applied to yield a weight average (over the whole distribution) molar mass of 7.1 × 106 g mol−1, in complete agreement with size exclusion chromatography coupled with multi-angle light scattering (SEC-MALS), which yielded a value of 7.2 × 106 g mol−1. Sedimentation velocity profiles show mucin to be very polydisperse, with a broad molar mass distribution obtained using the Extended Fujita algorithm, consistent with the elution profiles from SEC-MALS. On-line differential pressure viscometry coupled to the SEC-MALS was used to obtain the intrinsic viscosity [η] as a function of molar mass. These data combined with sedimentation coefficient data into the global conformation algorithm HYDFIT show that PIM has a flexible linear structure, with persistence length Lp ~10 nm and mass per unit length, ML ~2380 g mol−1 nm−1, consistent with a Wales-van Holde ratio of ~1.2 obtained from the concentration dependence of the sedimentation coefficient. Springer 2016-01-31 Article PeerReviewed Almutairi, Fahad M., Cifre, Jose-Gines Hernandez, Adams, Gary G., Kök, M. Samil, Mackie, Alan R., de la Torre, Jose Garcia and Harding, Stephen E. (2016) Application of recent advances in hydrodynamic methods for characterising mucins in solution. European Biophysics Journal, 45 (1). pp. 45-54. ISSN 1432-1017 Mucin; Molar mass; Conformation; Novel hydrodynamic methods http://link.springer.com/article/10.1007%2Fs00249-015-1075-0 doi:10.1007/s00249-015-1075-0 doi:10.1007/s00249-015-1075-0
spellingShingle Mucin; Molar mass; Conformation; Novel hydrodynamic methods
Almutairi, Fahad M.
Cifre, Jose-Gines Hernandez
Adams, Gary G.
Kök, M. Samil
Mackie, Alan R.
de la Torre, Jose Garcia
Harding, Stephen E.
Application of recent advances in hydrodynamic methods for characterising mucins in solution
title Application of recent advances in hydrodynamic methods for characterising mucins in solution
title_full Application of recent advances in hydrodynamic methods for characterising mucins in solution
title_fullStr Application of recent advances in hydrodynamic methods for characterising mucins in solution
title_full_unstemmed Application of recent advances in hydrodynamic methods for characterising mucins in solution
title_short Application of recent advances in hydrodynamic methods for characterising mucins in solution
title_sort application of recent advances in hydrodynamic methods for characterising mucins in solution
topic Mucin; Molar mass; Conformation; Novel hydrodynamic methods
url https://eprints.nottingham.ac.uk/42720/
https://eprints.nottingham.ac.uk/42720/
https://eprints.nottingham.ac.uk/42720/