Effect of Methyl Substitution Pattern on Methylcellulose Solution Behavior and Multiscale Structure 

Methylcellulose (MC) is a cellulose derivative where some hydroxyl groups are replaced with methoxy groups. Aqueous solutions of MC are widely used as additives in foods, construction materials, and biomedical applications, as they undergo thermoreversible gelation at elevated temperatures. MC is typically synthesized using techniques that yield a degree of substitution (DS) around 1.8, with a random substitution of methoxy groups along the chain. However, alternative synthesis methods can yield MC with varying heterogeneity in substitution patterns, which have been shown to impact the gelation temperature of MC. However, the MC chains’ multiscale structure in solution, around and above the gelation temperature, with alternative substitution patterns, is largely unknown. Elucidating this relationship between degree and pattern of substitution in MC chains and the resulting self-assembled structure and gelation temperature will be valuable and can guide MC synthesis tailored for specific applications. In this work, we develop a coarse-grained (CG) model for MC with force field parameters determined from atomistic simulations and from Bayesian optimization to match experimental gelation temperatures. We then use the CG model in molecular dynamics simulations to systematically investigate the impact of the degree and pattern of substitution on the self-assembly of MC chains in aqueous solution.