Nanoscale intermolecular interactions between human serum albumin and low grafting density surfaces of poly(ethylene oxide)

The net nanoscale interaction between a probe tip covalently bound with the blood plasma protein human serum albumin (HSA) and a surface of end-grafted poly(ethylene oxide) (PEO) mushrooms (M-n similar to 50K, Flory radius R-F similar to 9 nm, contour length L-contour similar to 393 nm) was measured directly on approach (loading) and retract (unloading) in aqueous buffer solution using the technique of high-resolution force spectroscopy (HRFS). On approach of the HSA probe tip to the PEO surface, a monotonic nonlinear repulsive net force was observed for tip-sample separation distances of <30 nm, the magnitude of which is much larger than that predicted by either electrostatic double layer or steric theories based on configurational entropy. Attractive contacts between the PEO and HSA are formed during experimentation, enabling the tethering and extension of individual PEO chains on retraction. The mean binding force of the HSA probe tip to individual PEO chains was determined to be <F-adh> = 0.06 +/- 0.10 nN or <F-adh/Radius> = 0.9 +/- 1.6 mN/m (where Radius is the end radius of the probe tip as measured by scanning electron microscopy). By combining the results of HRFS experiments with theoretical approaches, we have shown that this technique is a valuable tool for understanding biocompatibility at the nanoscale and can provide valuable information that may be used as a guideline for the design of improved synthetic macromolecular systems for future biomedical applications.