Modeling Collagen-Proteoglycan Structural Interactions in the Human Cornea
The cornea is a supremely organized connective tissue making it ideal for modeling and probing possible roles of collagen-PG interactions in the extracellular matrix. The cornea can be viewed as a reinforced electrolyte gel involving molecular-scale interactions between collagen fibrils, proteoglycans (PGs) and the mobile ions in the interfibrillar space. The swelling property of the tissue cannot be adequately predicted by Donnan theory for osmotic pressure. We propose an alternative unit cell approach based on a thermodynamic framework that employs a mean-field approximation for the electrostatic free energy and which accounts for a non-uniform electrostatic potential. The model is used to show that the equilibrium swelling pressure can be explained when the geometrical effect of electrolyte exclusion due to collagen fibril volume is considered. The model is further refined by dividing the PGs into collagen fibril coating and volumetric partitions. The model suggests that the PG coatings overlap at low hydration and set up repulsive forces that may act to maintain the collagen lattice order. Finally, we introduce a molecular-level unit cell in which volumetric domains within the unit cell are associated with the macromolecular GAGs and results from the continuum and molecular-level models are compared.
KeywordsCollagen Fibril Helmholtz Free Energy Keratan Sulfate Corneal Stroma Fixed Charge Density
This research was supported by the Stanford University Bio-X Interdisciplinary Initiatives Program (PMP), which is gratefully acknowledged. XC also received support from a Stanford Graduate Fellowship.
- Elliott GF, Hodson SA (1998) Cornea, and the swelling of polyelectrolyte gels of biological interest. Rep Math Phys 61:1325–1365 Google Scholar
- Scott JE (1992) Morphometry of cupromeronic blue-stained proteoglycan molecules in animal corneas, versus that of purified proteoglycans stained in vitro, implies that tertiary structures contribute to corneal ultrastructure. J Anat 180:155–164 Google Scholar