We employ quartz crystal microgravimetry with dissipation (QCM-D) and optical waveguide lightmode spectrometry (OWLS) to investigate the formation of polyelectrolyte multilayer films designed for cell contacting applications. Films are formed via the alternate, layer-by-layer assembly of positively and negatively charged biological polymers, such as polysaccharides and polyamino acids. The physical properties of the multilayer films – thickness, areal mass, degree of hydration, and elastic modulus – can be controlled through the solution salt concentration and post-formation chemical cross-linking steps, e.g. through the EDC-NHS method. Different cell-contacting applications demand different film properties. In particular, cell behavior is often strongly coupled to substrate hydration degree and elastic modulus. We show that decreasing salt concentration and/or conducting cross-linking steps can yield decreased film hydration and increased film elastic modulus. Preliminary hepatocyte culture results suggest a high degree of sensitivity of cell viability to film properties, as well as the overall potential of multilayer films in liver tissue engineering applications.