Sending and receiving signals is the basis of cell communication. Cell surface receptors react to a multitude of signal molecules and trigger cellular responses that, in turn, regulate organismal homeostasis. The malfunction of receptors and signals in cells may lead to the development of many diseases, including cancer, diabetes, neurodegeneration or autoimmune disorders. Specifically, the epidermal growth factor receptor (EGFR), which is activated after binding of the epidermal growth factor (EGF), is involved in the pathogenesis and progression of various carcinoma types. Moreover, it has been proven that the clustering of this receptor plays an important role in the activation of the cells. Thus, understanding this complex signal pathway is key for future therapeutic approaches and drug development. In addition, a tool capable of bridging this molecular event, that occurs at the nanoscale, with the cellular responses, measurable at the micro and mesoscale, is needed.
We aimed to develop a microfluidic platform to mimic closer the natural cell environment for the study of early EGFR-EGF signaling cascade in epithelial breast cancer cells. To this end we applied a technology recently developed that is based on the use of DNA origami nanostructures as molecular pegboards for presenting ligands to cells with a full control of their absolute number, stoichiometry and nanoscale orientation.