This paper presents the use of the localized surface plasmon resonance (LSPR) sensor concept to probe the formation of macroscopic and laterally mobile supported lipid bilayers (SLBs) on SiOx-encapsulated nanohole-containing Au and Ag films. A comparison between Au- and Ag-based sensor templates demonstrates a higher sensitivity for Au-based templates with respect to both bulk and interfacial refractive index (RI) changes in aqueous solution. The lateral mobility of SLBs formed on the SiOx-encapsulated nanohole templates was analyzed using fluorescence recovery after photobleaching (FRAP), demonstrating essentially complete (>96%) recovery, but a reduction in diffusivity of about 35% compared with SLBs formed on flat SiOx substrates. Furthermore, upon SLB formation, the temporal variation in extinction peak position of the LSPR active templates display a characteristic shape, illustrating what, to the best of our knowledge, is the first example where the nanoplasmonic concept is shown capable of probing biomacromolecular structural changes without the introduction of labels. With a signal-to-noise ratio better than 5 x 10(2) upon protein binding to the cell-membrane mimics, the sensor concept is also proven competitive with state-of-the-art label-free sensors.