Effect of Methylcellulose Chain Design on Gelation and Fibril Structure Using Coarse-Grained Modeling

Aqueous solutions of methylcellulose (MC) undergo thermoreversible gelation making them useful as additives for formulations with desired rheological properties. This gelation occurs at elevated temperatures and concurrently with the formation of stiff, high aspect ratio fibrils composed of several MC chains. The sol–gel transition temperature as well as the fibrillar structure of the gel state can be controlled by the molecular weight of the MC chains, MC concentration, and the design of the MC chains. One such MC design parameter is the degree of substitution (DS) which varies between 0 (cellulose) to 3.0 (fully methylated cellulose chain). The DS of commercially available MC (e.g., International Flavors and Fragrances’ Methocel A) is ∼1.8. The DS as well as the pattern of methylation (i.e., homogeneous or heterogeneous substitution) along the MC backbone can be tailored using variations in the synthesis protocols. To elucidate the effect of these MC chain design parameters on the sol–gel transition and the fibrillar structure of the MC chains, we conducted a multiscale computational study. First, we developed a coarse-grained (CG) model for MC with the model’s bonded parameters informed from atomistic simulations using Boltzmann inversion and nonbonded parameters informed from previous experimental studies of aqueous MC sol–gel phase behavior using surrogate Bayesian optimization. We performed molecular dynamics (MD) simulations of aqueous MC solutions with this CG model and characterized the effect of DS and methylation pattern on the gelation temperature and the MC chains’ fibril structure, specifically fibril diameter and persistence length. Fibril diameters and persistence lengths in our simulated systems agree well with those found from previous small-angle scattering analysis and electron microscopy measurements, providing validation for the results from the CG MD simulations. Using these CG MD simulations, we span a large MC design parameter space and identify these key design rules: (i) Aqueous solutions with MC chains having larger heterogeneity in the DS along the chain backbone, will gel at lower temperatures and assemble into fibrils with a smaller diameter. (ii) As the DS becomes “blockier” along the MC backbone, gelation will occur at lower temperatures, and fibril diameters will decrease. We expect our model development and the above design rules will aid future work focused on synthesis and/or simulation of MC with tailored gel properties for desired applications.