Critical Areas of Proliferation of Single Cells on Micropatterned Surfaces and Corresponding Cell Type Dependence

Material cues to influence cell proliferation are a fundamental issue in the fields of biomaterials, cell biology, tissue engineering, and regenerative medicine. This paper aims to investigate the proliferation of single mammal cells on micropatterned material surfaces. To this end, we prepared cell-adhesive circular microislands with 20 areas on the nonfouling background and systematically examined adhesion and proliferation behaviors of different kinds of single cells (primary stem and nonstem cells, cancer and normal cell lines) on micropatterns. On the basis of the analysis of experimental data, we found two critical areas about cell proliferation: (1) the critical spreading area of cells from almost no proliferation to confined proliferation, denoted as AP and (2) the critical spreading area of cells from confined proliferation to almost free proliferation, denoted as AFP. We further summarized the relative size relationship between these two critical areas and the characteristic areas of cell adhesion on both patterned and nonpatterned surfaces. While proliferation of single primary cells was affected by cell spreading, those cell lines, irrespective of normal and cancer cells, did not exhibit significant cell-spreading effects. As a result, this study reveals that proliferation of single cells is dependent upon spreading area, in particular for primary cells on material surfaces