Nanopatterned brushes of a thermo-responsive polymer, poly(2-(2-methoxyethoxy)ethyl methacrylate) (PMEO2MA), displaying a collapse temperature in the physiological range were synthesized for grafting diameters from a few micrometers down to 35 nm. The reversible collapse transition of the nanobrushes was studied in water as a function of their lateral confinement, down to ensembles of brushes containing only approximately 300 chains. The confinement results in a considerable broadening of the collapse transition and in an increase of the degree of vertical swelling, which can be explained by the internal structure of the nanodroplets derived from a theoretical model of dry nanobrushes. These results enable the rational design of responsive surfaces having a tunable topography engineered at the nanometer scale, which is of direct interest for the development of soft nanoactuators and new substrates for cell adhesion studies.