In this work, we analyze the impact of a chip coating with a self-assembled monolayer (SAM) of (3-aminopropyl)­triethoxysilane (APTES) on the electronic and mechanical properties of neuroelectronic interfaces. We show that the large signal transfer, which has been observed for these interfaces, is most likely a consequence of the strong mechanical coupling between cells and substrate. On the one hand, we demonstrate that the impedance of the interface between Pt electrodes and an electrolyte is slightly reduced by the APTES SAM. However, this reduction of approximately 13% is definitely not sufficient to explain the large signal transfer of APTES coated electrodes demonstrated previously. On the other hand, the APTES coating leads to a stronger mechanical clamping of the cells, which is visible in microscopic images of the cell development of APTES-coated substrates. This stronger mechanical interaction is most likely caused by the positively charged amino functional group of the APTES SAM. It seems to lead to a smaller cleft between substrate and cells and, thus, to reduced losses of the cell’s action potential signal at the electrode. The disadvantage of this tight binding of the cells to the rigid, planar substrate seems to be the short lifetime of the cells. In our case the density of living cells starts to decrease together with the visual deformation of the cells typically at DIV 9. Solutions for this problem might be the use of soft substrates and/or the replacement of the short APTES molecules with larger molecules or molecular multilayers.