The spatial arrangement of cells in their microenvironment is known to significantly influence cellular behavior, thus making the control of cellular organization an important parameter of in vitro co-culture models. However, recent advances in micropatterning co-culture methods within biochips do not address the simultaneous cultivation of anchorage-dependent and non-adherent cells. To address this methodological gap we combine S-layer technology with microfluidics to pattern co-cultures to study the cell-to-cell and cell-to-surface interactions under physiologically relevant conditions. We exploit the unique self-assembly properties of SbpA and SbsB S-layers to create an anisotropic protein nanobiointerface on-chip with spatially-defined cytophilic (adhesive) and cytophobic (repulsive) properties. While microfluidics control physical parameters such as shear force and flow velocities, our anisotropic protein nanobiointerface regulates the biological aspects of the co-culture method including biocompatibility, biostability, and affinity to non-adherent cells. The reliability and reproducibility of our microfluidic co-culture strategy based on laminar flow patterned protein nanolayers is envisioned to advance in vitro models for biomedical research.
- Biosensor Technologies
- S-layer proteins; self-assembly; microfluidics;laminar flow patterning;micro-patterned co-cultures