This paper presents a hypothesis relating the exclusion of a molecule (solute) from the surface of a protein in aqueous solution with the ability of that molecule to render surfaces "protein-resistant", that is, resistant to the adsorption of proteins from aqueous buffer. While few current data test this hypothesis, it does suggest that surfaces presenting groups derived from certain osmolytesmolecules synthesized by cells to relieve osmotic stresswill be protein-resistant. These predictions were tested by constructing protein-resistant, self-assembled monolayers (SAMs) based on the osmolytes betaine and taurine. Examination of data from the literature also revealed that most of the known protein-resistant surfaces are based on displays of kosmotropesmolecules that stabilize the native structure of proteins. The connection between protein resistance, kosmotropicity, and biological function as an osmolyte may illuminate all three properties.
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