Viscoelastic models of cells often treat cells as homogeneous objects. However, studies have demonstrated that cellular properties are local and can change dramatically based on the location being probed. Since membrane receptors are linked in various ways to the intracellular space, with some receptors linking to the cytoskeleton and others diffusing freely without apparent linkages, it is expected that the cellular physical response to mechanical stresses depends on the receptor being engaged. This study tested the hypothesis that cellular mechanical stiffness as measured via cytoskeletally-linked receptors are greater than stiffness measured via receptors that are not cytoskeletally-linked. A magnetic micromanipulator applied linear stresses to magnetic beads attached to living cells via selected receptors. One of the receptor classes being probed, the dystroglycan receptors, is linked to the cytoskeleton, while the other, the transferrin receptors, is not. Fibronectin-coated beads were used to test cell mechanical properties of the cytoskeleton without membrane dependence by allowing the beads to endocytose. For epithelial cells, transferrin-dependent stiffness and the endocytosed bead-dependent stiffness were similar, while the dystroglycan-dependent stiffness was significantly lower. For smooth muscle cells, dystroglycan-dependent stiffness was similar to the endocytosed bead-dependent stiffness, while the transferrin-dependent stiffness was lower. The conclusion of this study is that the measured cellular stiffness is critically influenced by specific receptor linkage and by cell type and raises the intriguing possibility of the existence of separate cytoskeletal networks with distinct mechanical properties that link different classes of receptors.