The identification of design criteria for the prevention of surface fouling by protein adsorption has been an elusive research goal. The current ideas in this domain assume two different directions. One focuses on correlating protein adsorption with macroscopic surface properties such as the water wettability. The second approach involves tailoring the molecular interactions between the adsorbing proteins and the surface. In this paper, we focus on the experimental results and theoretical ideas concerned with tuning the interfacial forces by means of terminally grafted PEO chains.

The surface force apparatus was used to measure directly the molecular forces between streptavidin and lipid bilayers displaying grafted M r 2,000 poly(ethylene glycol) (PEG). These measurements provide direct evidence for the formation of relatively strong attractive forces between PEG and protein. At low compressive loads, the forces were repulsive, but they became attractive when the proteins were pressed into the polymer layer at higher loads. The adhesion was sufficiently robust that separation of the streptavidin and PEG uprooted anchored polymer from the supporting membrane. These interactions altered the properties of the grafted chains. After the onset of the attraction, the polymer continued to bind protein for several hours. The changes were not due to protein denaturation. These data demonstrate directly that the biological activity of PEG is not due solely to properties of simple polymers such as the excluded volume. It is also coupled to the competitive interactions between solvent and other materials such as proteins for the chain segments and to the ability of this material to adopt higher order intrachain structures.Poly(ethylene glycol) (PEG) is used extensively to improve the biocompatibility of foreign materials for both in vivo and ex vivo applications (1-3). Its prevalent use is due largely to its low toxicity and low immunogenicity (1). In addition, due to its protein resistance, it is widely used as a stabilizing surface coating in biological environments (3-7). For example, PEG-functionalization of liposomes increased their blood circulation times by nearly an order of magnitude (4). In the clinic, ethylene oxide surface grafts are used to reduce protein adsorption onto the surfaces of biomedical polymers (1-3, 5-7). This is important for controlling the biological responses to the latter, in part, because protein adsorption is a well established first step in the humoral response against foreign materials (2,8,9). Thus, by preventing the unwanted adsorption of bioactive agents onto the surfaces of medical polymers, the surface grafting of hydrophilic polymers is one of the more effective, general strategies used to manipulate the biological activity of medical materials (3,(9)(10)(11)(12)(13)(14).The unusual efficacy of PEG as an apparently biologically passivating surface coating is linked to both the presumed biological inertness of the polymer backbone and to its solvated configuration (1, 3, 5, 7). In most cases, the proposed mechanisms for the protein resistance of PEG borrow from current theories for structureless polymers in isotropic liquids (5,(15)(16)(17)(18)(19). For example, PEG's ability to repel proteins is attributed to its large excluded volume (3,5,(15)(16)(17)(18)(19), its configurational entropy (20, 21), surface coverage by grafted chains (3,15,18), and the thickness of grafted layers (1,3,9,17,18). These latter attributes are all well described theoretically for both terminally anchored and soluble simple chains in simple solvents (22)(23)(24)(25). Based on ...

Terminally grafted chains of poly(ethylene glycol) (PEG) and oligo(ethylene glycol) reduce protein adsorption and cell adhesion on material surfaces. However, previous studies showed that protein−PEG adhesion is induced by the application of pressure. Because polymer behavior can vary with the molecular weight, in this study we directly measured the forces between streptavidin and end-grafted monolayers of PEG of different molecular weights and at grafting densities. The results of these measurements show that grafted PEG chains can exist in two different states:  a protein-repulsive state and a protein-attractive state. The attractive state can be induced not only by compression but also by increasing the temperature or by altering the polymer molecular weight. Both the critical applied load to induce the protein-attractive form of PEG and the relaxation time back to the protein-resistant state depend on the molecular weight of the grafted chains. The consequences of the observed behavior for the use of grafted PEG chains as protein antifouling coatings of biomaterials are discussed.

Poly(ethylene glycol) (PEG) has long been recognized for its unusual ability to resist protein adsorption. This is attributed to the repulsion of proteins by the polymer segments. Despite its successes, there are several reports that PEG does weakly bind proteins. This work tests the hypothesis that the PEG can bind to nonpolar, hydrophobic groups such as the aliphatic side chains of amino acids. To do this we measured the forcedistance profiles between PEG 5000 brushes and self-assembled alkanethiol monolayers with varying amounts of nonpolar methyl-terminal groups. The polymer adhesion to these chemically selective surfaces increased with increasing density of surface methyl groups. The equilibrium thickness of the polymer chains in contact with the alkanethiol monolayer decreased correspondingly. The brush did not adhere to lipid bilayers or to bare mica. The results show that PEG will adsorb to nonpolar, hydrophobic surfaces. These findings may provide a possible explanation for previous direct force measurements of protein-PEG adhesion, and reports of PEG complexation with partially folded proteins.

Two-dimensional polymers have numerous potential applications as surface coatings. In this work, we used the surface force apparatus to investigate the interfacial properties of monomeric and polymerized Langmuir−Blodgett films of the diacetylene 10,12-pentacosadiynoic acid (PCA). Using direct force and contact angle measurements, we investigated the impact of polymerization and film preparation conditions on the molecular surface properties of the layers. Humidity-dependent variations both in the water contact angles and in the directly measured interfacial energies of these layers were used to assess the film stability under different environmental conditions. Direct force measurements demonstrated directly that polymerization prevents molecular reorientations and consequent changes in the interfacial properties of the polymer films. Further, the polymerized diacetylene layers were stable to repeated subjection to large compressive loads over a course of several hours. A major limitation of the low-dimensional diacetylene polymers prepared from PCA is the difficulty of forming homogeneous, defect-free films over large areas. Our findings further demonstrate directly the impact of such heterogeneity on the interfacial properties of both monomeric and polymerized diacetylene films.