The tunable mechanical and physical properties of polydimethylsiloxane (PDMS) are commonly utilized for studying cellular dynamics. However, the inherent hydrophobic nature of PDMS limits its application as a cell culture film. Various surface modification techniques render PDMS films hydrophilic, altering their surface chemistry, elasticity, roughness and the cell attachment of anchorage-dependent cell types to the films. The surface properties of thin films lead to the alteration of the biomechano-physical properties of cells, so they can be used as a mechanical signature for the viability testing of different types of cell, such as normal and cancerous ones. In this study, 3T3 fibroblast and HaCaT keratinocyte cells were grown on different pristine and oxidized PDMS compositions by varying their base-to-curing-agent ratios (w/w). The enhanced wettability favors the cell spreading and growth rate of both 3T3 and HaCaT cells, and it varies with the film's surface chemistry and elasticity. This study focuses on the importance of understanding how various surface modification methods, like oxygen plasma and piranha treatment, can impact cell-cell and cell-substrate interaction for different cell types, thereby assisting in the preparation of various PDMS-based biomedical devices. © 2017 IOP Publishing Ltd.