(337e) Geometrically Modulated Substrates Direct Cell Migration and Multicellular Assembly

Physical properties of extracellular matrix such as stiffness, topography and geometry have emerged as determinants and regulators of cell functions. Cell-matrix interaction studies have been facilitated by Micropatterning techniques. For example, PDMS-based micropillar and microneedle arrays were used for investigating cellular probing traction forces applied onto the substrates. However, these materials with fibrillar micropatterned surfaces form discrete contact with cells, which are often considered not biologically relevant. Here we made physiologically relevant devices by attaching a smooth thin film of the same material onto the micropatterned structures. Thus, cells get direct contact with the continuous surface thin film when grown on top of the film-terminated fibrillar devices. Remarkably, cells could still sense the geometry of the underlying structures. Cells displayed migratory patterns in consistent with the geometry of the patterns beneath the surface film; intracellular adhesions and cytoskeletons showed alignment with the patterns of materials beneath the surface film; multicellular assembly and invasion was also in correlation with the patterns of materials underlying the surface film. Inspired by the phenomena, we further controlled cell migration and multicellular assembly by engineering film-terminated fibrillar devices with varying underlying structures and patterns. Our film-terminated micropatterning technique is therefore essential not only for studying fundamental questions of cell-ECM interactions, but also for directing cell motion and multicellular assembly with biomedical applications.