Proteoglycans and the modulation of cell adhesion by steric exclusion

The hypothesis that cell aggregation may be driven by linear polymers in the matrix, particularly glycosaminoglycans, is revisited in light of more recent evidence. A model is proposed that extends the concept of steric exclusion to include a role in determining the directionality of cell migration and neurite extension. Recent literature is reviewed to support the conclusion that in living tissues the theoretical conditions for driving aggregation and migration by steric exclusion are met. The ability of a linear polymer to exclude cells is a function of its viscosity, which is optimum with glycosaminoglycans similar to chondroitin sulfate. It is ineffective with low viscosity glycosaminoglycans such as most heparin or heparan sulfate. Hyaluronic acid, a massive polymer, excludes cells poorly when present as an open matrix gel but forms an effective exclusion barrier when attached to the cell surface. According to a model for steric exclusion in organogenesis, when cells have a glycocalyx of linear polymer, they should disperse and migrate down a viscosity gradient of excluding matrix polymer; when they shed or internalize their surface coat in the continued presence of matrix, they should be excluded into a smaller volume and thus stimulated to aggregate. © 1993 wiley-Liss, Inc.