The present work reports on the development of a range of poly(methyl methacrylate)/poly(ethylene glycol) (PMMAPEG)-based materials, characterized by different elasticity moduli in order to study the influence of the substrate's mechanical properties on the response of human umbilical vein endothelial cells (HUVECs). To render the selected materials cell-interactive, a polydopamine (PDA)/gelatin type B (Gel B) coating was applied. Prior to the in vitro assay, the success of the PDA and Gel B immobilization onto the materials was confirmed using X-ray photoelectron spectroscopy (XPS) as reflected by the nitrogen percentages measured for the materials after PDA and Gel B deposition. Tensile tests showed that materials with E-moduli ranging from 37 to 1542 MPa could be obtained by varying the ratio between PMMA and PEG as well as the PEG molecular weight and its functionality (i.e. mono-methacrylate vs. di-methacrylate). The results after 1 day of cell contact suggested a preferred HUVECs cell growth onto more rigid materials. After 1 week, the material with the lowest E-modulus of 37 MPa showed lower cell densities compared to the other materials. No clear correlation could be observed between the number of focal adhesion points and the substrate stiffness. Although minor differences were found, these were not statistically significant. This last conclusion again highlights the universal character of the PDA/Gel B modification. The present work could thus be valuable for the development of a range of cell substrates requiring different mechanical properties in line with the envisaged application while the cell response should ideally remain unaffected.