Design of blood-compatible materials is one of the most important and urgent research topics in the medical field responding to requests for implanting materials and materials for regenerative therapy.1 Poly(2-methoxyethyl acrylate) (PMEA) [Fig. 1(a)] is one of the best blood-compatible polymers,2 and its blood compatibility has been characterized by using various approaches.3,4,5,6 Although PMEA is already being used for practical applications such as artificial lungs,7 the mechanism of the blood compatibility of PMEA is still not fully understood.
Figure 1. The difference between PMEA and non-blood-compatible polymers evidently appeared in the results of differential scanning calorimetry (DSC) measurements. The mixtures of PMEA and water showed the cold crystallization of water at around −50 °C, whereas mixtures of non-blood-compatible polymers and water did not display this feature, indicating that water hydrating PMEA may give rise to its blood compatibility.4,5 This idea was supported by the results of attenuated total-reflection infrared (ATR-IR) spectroscopy. Ide and coauthors reported that water molecules weakly bound to the primary hydration water may correspond to the cold-crystallizable water.8 Recently, based on ATR-IR measurements and ab initio calculations, Morita and co-workers suggested that water molecules, which may be responsible for the blood compatibility, interact weakly with the methoxy moiety of PMEA in an intermediate way.9
Although many have suggested that weakly bound hydrating water plays an important role in blood compatibility, there are only two studies on the strength of the interaction between PMEA and biomolecules. In these reports, the protein resistance of PMEA was revealed by an adsorption experiment of bovine serum albumin (BSA) and fibrinogen onto PMEA surfaces using a quartz-crystal microbalance (QCM) technique.6 In a comparison of PMEA with hydrophobic polypropylene (PP) and hydrophilic poly(2-hydroxyethyl methacrylate) (PHEMA), PMEA exhibited smaller adsorption amounts of BSA and fibrinogen and higher detachment rate constants for these two proteins, indicating that the blood compatibility cannot be explained simply by the affinity of the polymer surface to water.
To understand the mechanism of the blood compatibility of PMEA, the interaction between PMEA and biomolecules in water must be explored intensively. In general, interactions in water may stem from the interplay of several different kinds of forces, such as electrostatic interaction, van der Waals interaction, water-mediated force, and steric force.10,11 Therefore, to elucidate which force is responsible for the blood compatibility, we need direct observation of the force operating between PMEA and biomolecules.
In this work, for the first time, we performed, a direct observation of the interaction of protein molecules with both blood-compatible and non-blood-compatible polymers using atomic force microscopy (AFM), which has generally been applied to measure the interactions in water.12 Our focus was on the adhesion between polymer and protein molecules. We employed poly(n-butyl acrylate) (PBA) [Fig. 1(b)] as a contrastive example of non-blood-compatible polymer, because PBA does not exhibit blood compatibility and cold crystallization in DSC, although PBA does show a similar glass transition temperature as PMEA, indicating that their chain mobility is similar.5 Based on the results of the adhesion experiment with AFM and the adsorption experiment with QCM, we discuss the mechanisms of polymer-protein interactions and blood compatibility.