•We discuss the role of membranes in mechanotransduction.•The chemical composition of lipid membranes directly affects its nanomechanical properties.•We comment on the different experimental techniques able to probe membrane mechanics.•We describe how force spectroscopy using AFM can explore the nanomechanics of membranes.•We discuss the role of membrane tension on a variety of cellular physicochemical phenomena. The cell membrane is a highly complex designed material with remarkable physicochemical properties; comprised mainly of lipid moieties, it is capable of self-assembling, changing morphology, housing a range of distinct proteins, and withstanding electrical, chemical and mechanical perturbations. All of these fundamental cellular functions occurring within a 5nm thick film is an astonishing feat of engineering, made possible due to the interplay of a variety of intermolecular forces. Elucidating how the interactions within the chemically distinct partners influence the nanomechanical properties of the membrane is essential to gain a comprehensive understanding of a wide-variety of both force-triggered and force-sensing mechanisms that dictate essential cellular processes.