ZOOM seminar - Engineering biological systems modulating protein material interfaces at the nanoscale to control cell behavior

Proteins are the critical link that mediate how nanomaterials interact with cells to trigger cellular uptake, regulate cell behavior, and alter tissue function. In this seminar, I describe how proteins-nanomaterial interactions can be leveraged to program stem cell behavior and improve delivery of therapeutic nanoparticles. Specifically, we use nanolithography techniques to pattern nanoscale features composed of cell adhesion proteins on surfaces to modulate stem cell behavior. We demonstrate that confined, anisotropic nanofeatures can direct the formation of highly oriented actin cellular cytoskeletons within a defined shape factor. This controlled orientation results in a highly uniform and contractile cytoskeleton that allow one to enhance or alter the differentiation fate of human mesenchymal stem cells. In addition to arranging proteins into nanoscopic domains on surfaces, we leverage the intrinsic ability of proteins to form layers on a nanoparticle surface, known as a protein corona, to direct nanoparticles (NPs) to specific cell types. Conventionally protein coronas have been found to hinder/alter nanoparticle interactions with cells to increase clearance and limit NP targeting ability. Here, I will show that by having a defined and active protein corona we can enhance targeting of specific cancer cell populations and alter the pathway by which cells uptake the NPs, thereby opening new avenues to target cells with conjugation-free protein layers. Together these studies highlight how we can leverage proteinmaterial interfaces to improve cell interactions for myriad applications that include cancer therapeutic development, cellular engineering, and cell-based therapies.