The modulation of biological interaction with artificial surfaces is a vital aspect of biomaterials research. Perhaps the most challenging area is transplantation involving the introduction of stem cells into the body with their ability to differentiate; the response of stem cells to implanted biomaterials (or to the host tissue) provides a uniquely sensitive way to explore biocompatibility. An understanding of how to direct specific substratumcellular responses is critical for the development of future biomaterials (e.g., for prosthesis). Attachment and spreading of a cell to and on a substratum are the first part of the process that leads to the ultimate assimilation of the new cell or prosthesis with the host tissue. Together with conventional microscopy, I have exploited a uniquely powerful noninvasive optical technique (Optical Waveguide Lightmode Spectroscopy, OWLS) to quantify cell attachment and spreading of stem cells to artificial biomaterials, and determine how the cell environment (the substratum),the complex liquid medium bathing the cell, and the presence of congeners, influence attachment and spreading. My results highlight that quantitative characterisation of interfacial interactions, including their kinetics leads to uniquely new insight into cell-protein-material interactions. This knowledge will be doubtless be useful in the development of new generations of biomaterials with improved properties designed for specific applications.