Effects of Hydrophobicity and Electrostatic Charge on Complement Activation by Amino Groups

Some studies have demonstrated that amino groups, acting as nucleophiles, are potent activators of the complement system, but others not. To clarify these contradictory results, we examined complement activation on two series of NH2/CH3 and NH2/COOH mixed self-assembled monolayers (SAMs). NH2/CH3 mixed SAMs were not potent activators of the complement system regardless of the ratio of NH2/CH3 in mixed SAMs. Numerous serum proteins, such as albumin, were adsorbed onto those SAMs and formed a protein layer which inhibited access of C3b to amino groups. In contrast, much C3b and/or C3bBb were deposited on NH2/COOH mixed SAMs with similar to 50-60% NH2 density on the surface and SC5b-9 was found in serum exposed to this SAM, indicating activation of the complement system. These results suggest that C3b can easily access nucleophilic NH2 groups because of the decrease in electrostatic interaction between negatively charged proteins and the NH2 SAM surface.