Cell-Cell Adhesion Driven Contact Guidance and its Effect on hMSC Differentiation.

Contact guidance has been extensively explored using patterned adhesion functionalities that predominantly mimic cell-matrix interactions. Whether similar contact guidance can be driven by other types of interactions, such as cell-cell adhesion, still remains a question. Herein, we address this query by engineering a set of microstrip patterns of (i) cell-cell adhesion ligands and (ii) segregated cell-cell and cell-matrix ligands, as a simple yet versatile set of platforms for the guidance of spreading, adhesion, and differentiation of mesenchymal stem cells. We found, for the first time to the best of our knowledge, that micropatterns of cell-cell adhesion ligands can induce contact guidance. Surprisingly, we found that patterns of alternating cell-matrix and cell-cell strips also induce contact guidance despite providing a spatial continuum for cell adhesion. We believe that this guidance is due to the difference between the potencies of the two adhesions. Furthermore, we found that patterns that combine the two segregated adhesion functionalities induce more human mesenchymal stem cell osteogenic differentiation than monofunctional patterns. This work provides a new insight into the functional crosstalk between cell-cell and cell-matrix adhesions and overall, further highlights the ubiquitous impact of the biochemical anisotropy of the extracellular environment on cell function.