Mechanisms of gel formation in collagen/hydroxypropyl methylcellulose aqueous mixtures below the threshold for macroscopic phase separation

The gelation mechanisms of aqueous collagen/hydroxypropyl methylcellulose (HPMC) mixtures were investigated below the macroscopic phase separation threshold. This study examines the interactions between collagen and HPMC, the phase behavior, and the resulting gel and structural properties. The results indicate that at low mixing concentrations, hydrogen bonding between collagen and HPMC, along with excluded volume effects, induces microscopic phase separation under partially phase-compatible conditions. As the HPMC concentration increases, the phase morphology transitions from a collagen-dominant phase to an HPMC-dominant phase, accompanied by enhanced hydrogen bonding between the two components. Gel formation in these mixtures follows a two-step gelation process, with HPMC influencing gelation kinetics. The excluded volume effect results in collagen concentration, while an optimal HPMC concentrations facilitates the entanglement of collagen chains, promoting the formation of α-helix, β-turn, and antiparallel β-sheet conformations, and ordered triple-helix structures, thereby enhancing gel properties. However, at excessively high HPMC concentrations, excessive hydrogen bonding and excluded volume effects hinder the formation of triple-helix structures, leading to a gel network with reduced mechanical properties. This study highlights the critical role of HPMC concentration in modulating collagen gel formation and provides insights into the complex interactions governing gelation in protein-polysaccharide systems.