Light Scattering Analysis of Mono- and Multi-PEGylated Bovine Serum Albumin in Solution: Role of Composition on Structure and Interactions.

The effect of polymer conjugation on the interactions between proteins in solution is evaluated by systematic analysis of the second virial coefficient (A2) for the particular example of single- and double-PEGylated bovine serum albumin (PEG-BSA) in dilute PBS solution. The effect of PEGylation on A2 is found to sensitively depend on both the composition and the distribution of PEG segments within the conjugate. Most importantly, at a given PEG volume fraction, A2 significantly increases with the degree of polymerization of tethered chains. Hence, a lesser number of long chains is more effective in solubilizing BSA than a correspondingly larger number of short chains. Analysis of the hydrodynamic radii of protein-PEG conjugates suggests that the increased solubility is concurrent with a structural transition in the case of high molecular PEG grafts that results in compact core-shell-type structures. The results reveal a link between the composition, structure, and solubility of polymer conjugates that might benefit the understanding of their biochemical characteristics and their design for functional material applications.