Molecular structure and interactions in carrageenan-gelatin complexes: A combined computational and experimental study

Abstract

Gelatin, a biopolymer derived from collagen, is extensively employed in biomedical and food applications due to its biocompatibility and gel-forming properties. However, its physicochemical behavior is highly dependent on structural state, being a function of amino acid composition, molecular weight distribution, and processing conditions. The formation of polyelectrolyte complexes with polysaccharides, such as carrageenans, can significantly alter gelatin’s conformational stability and functional performance. In this work, we investigated the interactions between fish gelatin and sulfated polysaccharides carrageenans (κ-, ι-, and λ-types) at the molecular level using integrated computational and experimental approaches. Molecular docking and molecular dynamics simulations were applied to analyze the effect of carrageenan type, length, and charge on the structure and stability of polysaccharide-gelatin complexes, as well as on the dynamics and stability of gelatin molecule at acidic and neutral pH. This paper presents the first systematic comparison of the interaction of fish gelatin with all three types of carrageenans (k-, k- and λ-) at the molecular level and shows for the first time that carrageenans can form complexes with gelatin molecules of different stoichiometry (1:1, 1:2 and 1:3 carrageenan: gelatin). The complementary zeta potential analysis confirmed the pH-dependent charge neutralization upon complexation, supporting the MD-predicted electrostatic-driven association. Scanning electron microscopy demonstrated microstructural reorganization in composite gels as a result of strong carrageenan-gelatin interaction. These findings have highlighted the critical role of molecular structure and electrostatic complementarity in gelatin-carrageenan hydrogels and contribute to the rational design of gelatin-based gel systems with desired properties.