Thermodynamic perspectives on the molecular mechanisms providing protein adsorption resistance that include protein-surface interactions.

Current theories regarding the molecular mechanisms that provide protein adsorption resistance primarily focus on the characteristics of various types of surface-tethered chains and their interactions with water but often neglect their interactions with the protein. Such theories thus do not provide a complete explanation for protein adsorption resistance. The real issue that must be addressed is which properties enable surfaces to interact with water more favorably than with proteins. To address this issue, a thermodynamic treatment of protein adsorption to surface-tethered chains is presented and specific molecular-level interactions are addressed that contribute to enthalpy, entropy, and free energy changes that are involved during protein adsorption processes. Based on this analysis, it is proposed that two independently controllable sets of criteria provide conditions that are thermodynamically favorable for protein adsorption resistance: (1) well-hydrated long flexible surface-tethered chains with packing density sufficiently low to allow chain mobility while still providing complete surface coverage, and (2) surface-tethered chains that contain hydrogen-bondable groups that are readily accessible to water molecules but not to the hydrogen bond-forming groups of a protein.