This study has been carried out to determine how the 3D microenvironment affects the complex functionality of the cells growing in it. The effect has been quantified in terms of albumin secretion from hepatic cells in this particular case to find which out of the three environmental cues (spatial, biophysical and biochemical) is the most dominant and which are redundant, if any. Inclusion of just the minimal essential cues would simplify the platform architecture making it cost effective and increasing its adaptability to the high throughput screening (HTS) format. Another objective is to find a biomarker associated with this physiological relevance which can act as an early indicator and diagnose if the tissue is on a trajectory toward physiological relevance or not. Equipped with the knowledge of the optimum microenvironment composition, one can engineer a 3D model that closely emulates the native tissue and would provide more predictive outcomes during the drug discovery and screening process.