Supramolecular protein-mediated assembly of brain extracellular matrix glycans.

Background: Hyaluronic acid (HA) is the major component of the extracellular matrix in the central nervous system and the only supramolecular glycosaminoglycan. Much focus has been given to using this high molecular weight polysaccharide for tissue engineering applications. In the majority of cases, HA is covalently functionalized with moieties that can facilitate network formation through physical selfassembly, or photo-catalyzed covalent crosslinking as the polysaccharide does not gel on its own. However, these covalent crosslinks are not the driving force of HA self-assembly in biological tissues. Methods: Oscillatory rheology and dynamic light scattering were used to study albumin/HA structures. Dynamic light scattering and transmission electron microscopy were used to study albumin/chondroitin sulfate (CS) structures. UV-vis spectroscopy was used to study mass transfer of a hydrophilic small molecule into the albumin/HA/CS materials. Results: In this work we examine the intermolecular interactions of two major glycans found in the human brain, HA and the lower molecular weight CS , with the protein albumin. We report physiochemical properties of the resulting supramolecular micro- and nanomaterials. Albumin/HA mixtures formed supramolecular gels, and albumin/CS mixtures formed micro- and nanoparticles. We also summarize the concentrations of HA and CS found in various mammalian brains. Conclusions: Simple preparation and combination of commercially available charged biomacromolecules under short time-scales can result in interesting self-assembled materials with structures at the micron and nanometer length-scales. Such materials may have utility in serving as cost-effective and simple models of nervous system electrostatic interactions and as in vitro drug release and mass transfer quantification tools.