A stimuli responsive nanofiber that includes a stimuli responsive polymer, such as a thermally responsive polymer, and a cross-linking agent having at least two latent reactive activatable groups. The nanofiber may also include a biologically active material or a functional polymer. The stimuli responsive nanofiber can be used to modify the surface of a substrate. When the nanofiber includes a thermally responsive polymer, the physical properties of the surface can be controlled by controlling the temperature of the system, thus controlling the ability of the surface to bind to a biologically active material of interest.