Mutual Macromolecular Crowding in Polymer Solutions

Ogston and Laurent conceived and established a theory for steric exclusion of spherical particles such as globular proteins by a suspension of randomly oriented fibers. In their model, a protein can just touch the surface of a fiber, so the space occupied by the fiber itself, in addition to a cylindrical shell with a thickness equal to the radius of the protein, are spaces excluded to the protein. In a suspension of many fibers, the effective concentration of the protein is increased, because the available volume is reduced. This model was successfully applied to explain a number of properties (association and conformational equilibria, partition between compartments, osmotic pressure, etc.) for solutions of proteins in the presence of flexible polymers such as hyaluronan (HA), and the relevance of steric exclusion to the properties of biological tissues was established. Because small globular proteins are excluded only from a cylindrical shell immediately surrounding a linear HA chain, the crowding effect is sensitive to the mass concentration of the polymer segments, but not the molecular mass of the polymer chain. Matsuoka and Cowman subsequently developed a semi-empirical expression to quantitatively account for the concentration, shape, and molecular mass dependence of physicochemical properties (steady shear viscosity, osmotic pressure, light scattering, etc.) of HA or other polymer solutions. A connection between the Ogston-Laurent and Matsuoka-Cowman approaches will be presented, providing a firm foundation for understanding polymer solution properties on the basis of mutual macromolecular crowding, where steric exclusion depends on the effective hydrodynamic volume of the polymer. This theory can be employed to explain the dependence of amyloid protein fibril formation on the molecular mass of crowding polymers.