When materials are implanted into the body or introduced to body fluids ex vivo, such as for a blood test, serum protein binds to the surface and causes an inflammatory response via the Vroman cascade. Many different organic molecules have been used to reduce protein fouling, most notably polyethylene glycol (PEG). While there have been numerous experimental and modeling studies that have sought to document the mechanism by which protein adhesion inhibition occurs, the exact mechanism is still not known. It is generally agreed that most surfaces that exhibit protein resistance tend to be hydrophilic in nature, hydrogen-bond accepting, lacking hydrogen-bond donors, and electrically neutral in charge. Yet, not all biocompatible materials (materials resisting serum protein adhesion) may exhibit these characteristics. In order to more efficiently create feasible biomaterials, it is important to be able to quantify the electrostatic (ES), van der Waals (vdW), steric, and ‘hydrophobic' forces involved in protein adhesion rather than just characterizing them qualitatively.

In this study, self assembled monolayers (SAMs) were used to create surfaces with varying end groups for their characterization relating to protein resistance. SAMs are commonly used to study various functional groups for protein resistance since thiols easily coordinate with gold substrates at room temperature to form uniform monolayers. The homogeneous SAMs included alkane thiols with a methyl end group (hexadecane thiol), carboxylic end group (mercaptohexadecanoic acid), and hydroxyl end group (mercaptohexadecanol). These SAMs were examined using atomic force microscopy (AFM) to determine the interaction forces for SAM/SAM pairs as well as SAM/fouling protein pairs. The fouling protein used was bovine serum albumin (BSA). BSA was chosen because it has a 76 % similarity to human serum albumin, which is the most abundant serum protein and the first to bind in the Vroman cascade. Using AFM, it is possible to examine the forces that attract/repel proteins from the SAM surface (approaching curve) as well as the forces that are involved in the actual adhesion of the protein to a surface (retracting curve). Each of the forces involved in protein adhesion (including ES, vdW, steric, and ‘hydrophobic') have influence over different characteristic separation distances from the surface. The magnitude of these forces depends on the separation distance as well as the materials of interaction. The adhesion force data described above was interpreted in terms of these different forces, with a goal of identifying and characterizing the controlling force in the protein adhesion/adhesion inhibition process.