Ions in hyaluronic acid solutions.

Abstract

Hyaluronic acid (HA) is an anionic biopolymer that is almost ubiquitous in biological tissues. An attempt is made to determine the dominant features that account for both its abundance and its multifunctional role, and which set it apart from other types of biopolymers. A combination of osmotic and scattering techniques is employed to quantify its dynamic and static properties in near-physiological solution conditions, where it is exposed both to mono- and divalent counterions. An equation of state is derived for the osmotic pressure Pi in the semidilute concentration region, in terms of two variables, the polymer concentration c and the ionic strength J of the added salt, according to which Pi=1.4x10(3)c(9/4)/J(3/4) kPa, where c and J are expressed in mole. Over the physiological ion concentration range, the effect of the sodium chloride and calcium chloride on the osmotic properties of HA solutions is fully accounted for by their contributions to the ionic strength. The absence of precipitation, even at high CaCl(2) concentrations, distinguishes this molecule from other biopolymers such as DNA. Dynamic light scattering measurements reveal that the collective diffusion coefficient in HA solutions exceeds that in aqueous solutions of typical neutral polymers by a factor of approximately 5. This property ensures rapid adjustment to, and recovery from, stress applied to HA-containing tissue. Small angle x-ray scattering measurements confirm the absence of appreciable structural reorganization over the observed length scale range 10-1000 A, as a result of calcium-sodium ion exchange. The scattered intensity in the transfer momentum range q>0.03 A(-1) varies as 1/q, indicating that the HA chain segments in semidilute solutions are linear over an extended concentration range. The osmotic compression modulus c partial differential Pi/partial differential c, a high value of which is a prerequisite in structural biopolymers, is several times greater than in typical neutral polymer solutions.