Structural determinants of mucus barrier function: How chondroitin sulfate disaccharide composition modulates mucin binding and permeability

  • Int J Biol Macromol. 2026 Jun 24:373:153196. doi: 10.1016/j.ijbiomac.2026.153196.
Kangyu Wang  1 ,  Ping Yang  1 ,  Xiaojie Qin  1 ,  Yujie Guo  2 ,  Chunhui Zhang  3
Affiliations
  • 1. Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
  • 2. Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. Electronic address: [email protected].
  • 3. Key Laboratory of Agro-Products Processing, Ministry of Agriculture and Rural Affairs, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. Electronic address: [email protected].
PMID: 42342171 DOI: 10.1016/j.ijbiomac.2026.153196
Abstract

Chondroitin sulfate (CS) is a bioactive polysaccharide derived from animal cartilage that must pass through the intestinal mucus layer before epithelial absorption. We investigated the penetration behavior and mucus permeability effects of CS samples with distinct disaccharide compositions from bovine (BCS), chicken (CCS), and shark (SCS) cartilage. Using a mucus layer model, Mucin (MUC2) structure was observed to unfold and loosen upon binding with CS, accompanied by increased mucus viscoelasticity and reduced mucus permeability. Afterwards, binding affinity to MUC2 was found to be correlated positively with 4-chondroitin sulfate (CSA) content (BCS > CCS > SCS) and negatively with 6-chondroitin sulfate (CSC). Results of molecular dynamics suggested stronger CSA-MUC2 binding energy (-28.72 kcal/mol) than that of CSC (-20.8 kcal/mol), which was consistent with enhanced local MUC2 domain association and reduced pore like interfacial space. Overall, this study provides in vitro evidence that CS disaccharide composition may influence its interaction with MUC2 and the resulting changes in mucus permeability.

Keywords
Chondroitin sulfate; Molecular dynamics simulation; Mucus permeability; Polysaccharide-mucin interaction.
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