The lubrication properties of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) extended supported bilayers were studied and compared to those of surface-attached DSPC small unilamellar vesicles (liposomes) in order to elucidate the effect of phospholipid geometrical packaging on the lubrication and mechanical properties of these boundary layers. The topography and response to the nanoindentation of bilayer- and liposome-covered surfaces were studied by an atomic force microscope (AFM). In parallel, normal and shear (frictional) forces between two opposing surfaces bearing DSPC vesicles/bilayers across water were studied with the surface force balance (SFB). A correlation between nanomechanical performance in the AFM and stability and lubrication in the SFB was observed. Bilayers were readily punctured by the AFM tip and exhibited substantial hysteresis between approach and retraction curves, whereas liposomes were not punctured and exhibited purely elastic behavior. At the same time, SFB measurements showed that bilayers are less stable and less efficient lubricants compared to liposomes. Bilayers provided efficient lubrication with very low friction coefficients, 0.002-0.008 up to pressures of more then 50 atm. However, bilayers were less robust and tended to detach from the surface as a result of shear, leading to high friction for subsequent approaches at the same contact position. In contrast, liposomes showed reversible and reproducible behavior under shear and compression, exhibiting ultralow friction coefficients of μ ≈ 10(-4) for pressures as high as 180 atm. This is attributed to the increased mechanical stability of the self-closed, closely packed liposomes, which we believe results from the more defect-free nature of the finitely sized vesicles.