The significance of mechanical signals in cellular fate and function of anchorage-dependent cells is now widely established. This mechanosensitivity can be attributed, in part, to cellular adhesions, such as focal adhesions and adherens junctions, representing highly sensitive mechanosensors of remarkable plasticity. To date, the functional significance of this plasticity during cellular mechanosensing remains elusive. Further progress in this exciting field has been hindered by the availability of suitable artificial cell substrates of adjustable stiffness. Traditionally employed polymeric cell substrates with polymer-conjugated linkers are limited in their ability to mimic the dynamics and plasticity observed at cellular adhesion. To overcome these limitations, we present results from cell spreading/migration experiments on an alternative artificial cell substrate of adjustable stiffness, a polymer-tethered lipid multi-bilayer with N-cadherin linkers. Unlike linker-functionalized polymeric substrates, polymer-tethered lipid multi-bilayers allow the dynamic assembly of linkers into linker clusters underneath cellular adhesions without impairing cell spreading and migration. Experiments are discussed, which explore the influence of substrate stiffness, adjusted by the degree of bilayer stacking, on cell-substrate linker dynamics and distribution, as well as cytoskeletal organization and cellular traction forces. The presented experimental findings demonstrate that the N-cadherin-functionalized polymer-tethered multi-bilayer system is a powerful experimental platform that provides fascinating insight into the maturation and plasticity of cellular adhesions during cell spreading and migration in response to external mechanical stimuli.