Reversible Condensation of Mucins into Nanoparticles

Abstract

Mucins are high molar mass glycoproteins that assume an extended conformation and can assemble into mucus hydrogels that protect our mucosal epithelium. In nature, the challenging task of generating a mucus layer, several hundreds of micrometers in thickness, from micrometer-sized cells is elegantly solved by the condensation of mucins inside vesicles and their on-demand release from the cells where they suddenly expand to form the extracellular mucus hydrogel. We aimed to recreate and control the process of compaction for mucins, the first step toward a better understanding of the process and creating biomimetic in vivo delivery strategies of macromolecules. We found that by adding glycerol to the aqueous solvent, we could induce drastic condensation of purified mucin molecules, reducing their size by an order of magnitude down to tens of nanometers in diameter. The condensation effect of glycerol was fully reversible and could be further enhanced and partially stabilized by cationic cross-linkers such as calcium and polylysine. The change of structure of mucins from extended molecules to nano-sized particles in the presence of glycerol translated into macroscopic rheological changes, as illustrated by a dampened shear-thinning effect with increasing glycerol concentration. This work provides new insight into mucin condensation, which could lead to new delivery strategies mimicking cell release of macromolecules condensed in vesicles such as mucins and heparin.

Assembly Mechanism of Mucin and von Willebrand Factor Polymers

“…These simulations demonstrated that there are no topological or steric barriers to formation of the beaded filament by full-length MUC2 ( Figure 6 J) and that compact or expanded PTS regions can both be accommodated ( Figure S8 E). The former would correspond to pre-glycosylated or calcium-bound glycosylated condensed states ( Verdugo et al, 1987 ; Yan et al., 2018 ), whereas the latter would correspond to unfurled, hydrated states. A direct comparison of the simulations with measurements on polymers of secreted mucins cannot be made because the secreted polymers lack the filament scaffold of the assembly intermediate characterized in this work.…”

Mucin Thin Layers: A Model for Mucus-Covered Tissues

“…Different mechanisms have already been proposed to regulate the binding of molecules to mucin [31]. In general, the occurring mechanisms affect the fate of the particles facing and entering the mucus barrier and their mutual interaction may allow tuning the mucus gel properties, and strengthening or weakening the gel mesh [32,33].…”

Studi Termodinamika Transpor Ionik Natrium Klorida Dalam Air dan Campuran Tertentu

“…Massa Molar (137)(138)(139) Penampilan Densitas (140)(141)(142) Titik Lebur (143)(144)(145) Titik Didih (146)(147)(148) Kelarutan (149)(150)(151) Dalam Air (152)(153)(154) 58,44 g/mol Massa [222][223][224][225][226]…”