This experimental study explores the capture and manipulation of micrometer-scale particles by single surface-immobilized nanoparticles. The nanoparticles, approximately 10 nm in diameter, are cationic and therefore attract the micrometer-scale silica particles in an analyte suspension. The supporting surface on which the nanoparticles reside is negative (also silica) and repulsive toward approaching microparticles. In the limit where there are as few as 9 nanoparticles per square micrometer of collector, it becomes possible to capture and hold micrometer-scale silica particles with single nanoparticles. The strong nanoparticle−microparticle attractions, their nanometer-scale protrusion forward of the supporting surface, and their controlled density on the supporting surface facilitate microparticle−surface contact occurring through a single nanoelement. This behavior differs from most particle−particle, cell−cell, or particle (or cell)−surface interactions that involve multiple ligand−receptor bonds or much larger contact areas. Despite the limited contact of microparticles with surface-immobilized nanparticles, microparticles resist shear forces of 9 pN or more but can be released through an increase in the ionic strength. The ability of nanoparticles to reversibly trap and hold much larger targets has implications in materials self-assembly, cell capture, and sorting applications, whereas the single point of contact affords precision in particle manipulation.