Protein precipitation

Protein precipitation is widely used in downstream processing of biological products in order to concentrate proteins and purify them from various contaminants. For example, in the biotechnology industry protein precipitation is used to eliminate contaminants commonly contained in blood. The underlying mechanism of precipitation is to alter the solvation potential of the solvent, more specifically, by lowering the solubility of the solute by addition of a reagent.

The solubility of proteins in aqueous buffers depends on the distribution of hydrophilic and hydrophobic amino acid residues on the protein's surface. Hydrophobic residues predominantly occur in the globular protein core, but some exist in patches on the surface. Proteins that have high hydrophobic amino acid content on the surface have low solubility in an aqueous solvent. Charged and polar surface residues interact with ionic groups in the solvent and increase the solubility of a protein. Knowledge of a protein's amino acid composition will aid in determining an ideal precipitation solvent and methods.

Repulsive electrostatic forces form when proteins are dissolved in an electrolyte solution. These repulsive forces between proteins prevent aggregation and facilitate dissolution. Upon dissolution in an electrolyte solution, solvent counterions migrate towards charged surface residues on the protein, forming a rigid matrix of counterions on the protein's surface. Next to this layer is another solvation layer that is less rigid and, as one moves away from the protein surface, contains a decreasing concentration of counterions and an increasing concentration of co-ions. The presence of these solvation layers cause the protein to have fewer ionic interactions with other proteins and decreases the likelihood of aggregation. Repulsive electrostatic forces also form when proteins are dissolved in water. Water forms a solvation layer around the hydrophilic surface residues of a protein. Water establishes a concentration gradient around the protein, with the highest concentration at the protein surface. This water network has a damping effect on the attractive forces between proteins.

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