Free energy landscape of wrapping of lipid nanocluster by polysaccharides

Wrapping of a 20-mer cholesterol nano-cluster (CHL-nanoC) by two widely different types of beta-glucan polysaccharides (23-25 mers) having significantly varying glycosidic linkage patterns and side chains is studied by Well-Tempered MetaDynamics (WT-MetaD) simulations. The problem has its relevance in the faecal sterol and bile acid excretion in humans and the role of dietary fibres in aiding the process and combating dyslipidemia. Additionally, the distinctive collective variables studied here can be extended for modeling of polymer wrapped soft clusters/nano-particles in general. The wrapping ability is observed to be significantly correlated to the bending of the polysaccharide chain, an attribute of the glycosidic linkage type. By biasing two unique collective variables, the radius of gyration of the polysaccharide (Rg, poly) and the second order Legendre polynomial of the segment orientation parameter, theta, we could successfully observe the wrapping process. This work compares in detail the physical properties of the polysaccharide encapsulated CHL-nanoC by probing the radius of curvature (Rcurv, poly) of the polysaccharides, their coordination number with respect to the CHL-nanoC (CN), fractional CHL-nanoC surface coverage and the electrostatic surface potentials of the complex assembly. Results indicate that the beta-glucan having 1-4 glycosidic linked monomers with intermittent 1-3 linkage is able to wrap the CHLnanoC more effectively. The 1-3 glycosidic linked beta-glucan with 1-6 glycosidic bonds in side chains is significantly curled up and appears to be less efficient in wrapping the nanoC. This work provides a comparative molecular level picture of mutual interaction between two major dietary polysaccharide variants and lipid globules as indicated by numerous clinical level studies involving mice and human models.