Besides surface chemistry, the surface roughness on the micrometer scale is known to dominate the wetting behavior and the biocompatiblity properties of solid-state materials. The significance of topographic features with nanometer size, however, has yet to be demonstrated. Our approach is based on well-defined Ge nanopyramids naturally grown on Si(001) using ultrahigh vacuum chemical vapor deposition, where the nanopyramid density can be precisely controlled by the growth conditions. Since the geometry of the nanopyramids, often termed dome clusters, is known, the surface roughness can be characterized by the Wenzel ratio with previously unattainable precision. Dynamic contact-angle measurements and adsorption of gamma -globulin as a function of that ratio demonstrate the strong correlation between surface nanoarchitecture, on one hand, and wetting behavior and biocompatibility, on the other hand. Related x-ray photoelectron spectroscopy measurements reveal that potential changes of surface composition can be definitely excluded.