Direct Determination of Chitosan–Mucin Interactions Using a Single-Molecule Strategy: Comparison to Alginate–Mucin Interactions

Abstract

Aqueous chitosan possesses attractive interaction capacities with various molecular groups that can be involved in hydrogen bonds and electrostatic and hydrophobic interactions. In the present paper, we report on the direct determination of chitosan-mucin molecular pair interactions at various solvent conditions as compared to alginate-mucin interactions. Two chitosans of high molecular weight with different degrees of acetylation-thus possessing different solubility profiles in aqueous solution as a function of pH and two alginates with different fractions of α-guluronic acid were employed. The interaction properties were determined through a direct unbinding assay at the single-molecular pair level using an atomic force microscope. When probed against immobilized mucin, both chitosans and alginates revealed unbinding profiles characteristic of localized interactions along the polymers. The interaction capacities and estimated OPEN ACCESSPolymers 2015, 7 162 parameters of the energy landscapes of the pairwise chitosan-mucin and alginate-mucin interactions are discussed in view of possible contributions from various fundamental forces. Signatures arising both from an electrostatic mechanism and hydrophobic interaction are identified in the chitosan-mucin interaction properties. The molecular nature of the observed chitosan-mucin and alginate-mucin interactions indicates that force spectroscopy provides fundamental insights that can be useful in understanding the surface binding properties of other potentially mucoadhesive polymers.

A Synthetic Bioinspired Carbohydrate Polymer with Mucoadhesive Properties

“…This is particularly apparent at rupture lengths above 200 nm where P3 rupture force distributions include weight from a mean of 200 pN (Figure S17) while those of GlcPAS50 are below 80 pN. This observed mean rupture force of ≈200 pN agrees with previously reported values for chitosan and PGM at an identical tip retraction speed of 1 μm s −1 . Taken together, these data show that while P1 – P3 and GlcPAS50 are all capable of binding with mucin, P3 possesses a unique combination of positive charge and chain length that translates to significant mucoadhesivity.…”

“…We conjugated P1 – P3 , 2‐mercaptoethanol (2ME), and a thiol‐terminated 50‐mer neutral PAS (GlcPAS50) to gold‐coated AFM tips via thiol‐gold chemistry (Figure B) and performed repeated extension and retractions from a porcine gastric mucin (PGM) coated mica surface in 10 m m PBS buffer pH 7.4 (Figure S12). Hysteresis between the extension and retraction curves corresponds to adhesion events, which reflect intermolecular interactions at rupture lengths greater than 20 nm (Figure C). When comparing between tips on mucin‐functionalized surfaces, all four polymer functionalized tips exhibit significantly higher adhesion event probability than 2ME functionalized tips (0.5 average events per curve) as expected (Figure D).…”

A Synthetic Bioinspired Carbohydrate Polymer with Mucoadhesive Properties

“…This is particularly apparent at rupture lengths above 200 nm where P3 rupture force distributions include weight from am ean of 200 pN ( Figure S17) while those of GlcPAS50 are below 80 pN.T his observed mean rupture force of % 200 pN agrees with previously reported values for chitosan and PGM at an identical tip retraction speed of 1 mms À1 . [42] Taken together,these data show that while P1-P3 and GlcPAS50 are all capable of binding with mucin, P3 possesses au nique combination of positive charge and chain length that translates to significant mucoadhesivity.…”

“…Forf urther background, we direct the reader to two reviews (Newman, 2008 [40] and Hughes,2016 [41] )onthe SMFS technique.W econjugated P1-P3,2-mercaptoethanol (2ME), and at hiol-terminated 50-mer neutral PA S( GlcPAS50) to gold-coated AFM tips via thiol-gold chemistry ( Figure 3B) and performed repeated extension and retractions from ap orcine gastric mucin (PGM) coated mica surface in 10 mm PBS buffer pH 7.4 ( Figure S12). Hysteresis between the extension and retraction curves corresponds to adhesion events,w hich reflect intermolecular interactions at rupture lengths greater than 20 nm [42] (Figure 3C). When comparing between tips on mucin-functionalized surfaces,a ll four polymer functionalized tips exhibit significantly higher adhesion event probability than 2ME functionalized tips (0.5 average events per curve) as expected ( Figure 3D).…”

Microscopic Techniques for the Analysis of Micro and Nanostructures of Biopolymers and Their Derivatives

“…Particle dispersion Cellulose nanofiber [74] Particle Size Kondagogu gum biopolymer assisted Pt nanoparticles [24] Core shell structure Chitosan/PEO [75] TEM + selected area electron diffraction Crystallographic analysis Biopolymer assisted nanoparticles [21,24] Atomic force microscopy Molecular structure and conformation Xanthan gum [76][77][78] Nanomaterial topography Nanocellulose [79,80] Particle size and shape Nanocellulose [81] Chemical force microscopy Chemical interactions Chitosan [82] Magnetic force microscopy Magnetic properties Chitosan based magnetic nanohydrogels [83] Scanning tunneling microscopy Molecular structure Particle Size Surface modification…”