To study cellular responses in relation to the microenvironments, we have constructed a series of zwitterionic polymeric films and extracellular matrix protein conjugated lipid bilayer as the biomimetic cell culture platforms. In this talk, I will present the strategy of tunable materials design intending to closely mimic the in vivo microenvironment of cells. We identified a series of surface constructs, R3CE platform (Rapid, Rare Cell 3D Expansion) which could induce and maintain stemness of the cells, subsequently leading to single cell derived 3D spheroid within days. Clinical studies have indicated that extremely low abundant cells, such as primary tissues, circulating tumor cells, and stem cells, can be expanded to sufficient quantity for the subsequent multiomic molecular analysis and in vitro drug testing - an important step toward precision medicine.