Calcium destabilizes and causes conformational changes in hyaluronic acid.

The physical properties of proteoglycans found in the extracellular matrix influence the behavior of resident macromolecules, micro-ions, and cells. The forces stabilizing structured regions of hyaluronic acid (HA), a major component of extracellular matrix, were measured. The free energy of stability associated with structured regions within human HA was determined by potentiometric titration. A plot of free energy versus temperature demonstrated that the secondary structure was most stable at 25 degrees C and was destabilized at temperatures near 50 degrees C. In the presence of 5 mM CaCl2, the free energy of stability of the structured regions was reduced by 30 cal/mole. Classical light scattering and viscosity measurements confirmed the impact of calcium on HA. CaCl2 (5 mM) reduced the radius of gyration of HA. Above concentrations of 3 mM calcium, the viscosity of 0.1% HA solutions was reduced sharply. The ability of cells to secrete calcium, combined with the exquisite sensitivity of HA to calcium, may permit cell-mediated modification of the extracellular matrix and thus may facilitate cell motility.