Investigation on the Linker Length of Synthetic Zwitterionic Polypeptides for Improved Nonfouling Surfaces

Zwitterionic polymers are outstanding nonfouling materials widely used for surface modification. However, works that systematically evaluate the structure–activity relationship of the side chain linker effect with related antifouling abilities are sparse. Here, we generate a series of well-defined zwitterionic polypeptides bearing oligoethylene glycol (EG) linkers in the side chain (P(CB-EGxGlu), x = 1–3) and anchor them on gold surfaces via the grafting-to approach to compare their antifouling performances. The surface properties are characterized by X-ray photoelectron spectroscopy (XPS), circular dichroism spectroscopy (CD), variable angle spectroscopic ellipsometry (VASE), static water contact angle (SCA), and atomic force microscopy (AFM). By use of quartz crystal microbalance with dissipation (QCM-D), confocal microscopy, and scanning electron microscope, our results convincingly demonstrate the excellent antifouling performance of all zwitterionic polypeptides. Importantly, the surface coated with P(CB-EG3Glu), the one with the longest EG linker, exhibits the best resistance to single protein (below the detection limit of QCM) and blood serum (∼96–98% reduction) adsorption, which largely outperforms those of the PEG positive control and the two P(CB-EGxGlu) analogues with shorter EGx linkers. The same P(CB-EG3Glu) surface also gives the highest degree of prevention of cell/platelet/bacterial attachment (∼99% reduction) among all samples tested. Together, our study highlights the linker effect to the nonfouling performance of zwitterionic polypeptides, and the results strongly support P(CB-EG3Glu) as a robust nonfouling material for numerous applications.