Microtubules (MTs) are linked to cell mechanobiology. "Stable" and "dynamically unstable" microtubule (MT) subtypes are differentially sensitive to growth and distribution in serum starved (SS) versus full serum (FS) conditions. Atomic Force and Immunofluorescence microscopies were used to study the nanomechanical properties of the cell membrane in response to serum conditions and nocodazole. Nanomechanical properties of the cell membrane remain unchanged under SS/FS conditions even though there are drastic MT changes. The cell membrane is shown to depend on unstable MTs and the intermediate filament (IF) networks to maintain local stiffness. Measurements of local membrane nanomechanics in response to nocodazole display characteristic serum dependent decays. The responses suggest that the cell exists in a mechanical transition state. Stiffness is shown to depend on the interplay between dynamically unstable MTs, stable MTs and IFs which all act to impart a distinct cellular type of transient "metastability".