Materials technology has been an essential enabling tool for us both in terms of creating tissue-mimetic platforms for discovery and screening as well as creating entirely new materials that mimic regulatory principles found in nature. For example, we have modeled 3D cell migration using engineered hydrogels based on collagen I (Ulrich et al., Biomaterials 2010, 2011) and hyaluronic acid (Ananthanarayan et al., Biomaterials 2011). By photopatterning these hydrogels, we have been able to create new high-throughput platforms for mechanobiology that sample thousands of microenvironmental conditions on a single hydrogel (Rape et al., Nature Communications 2016).
An emerging but complementary direction in our lab has been to develop “smart” materials inspired by cytoskeletal networks within cells. Our efforts to date have centered around stimulus-responsive intrinsically disordered protein domains (IDPs) that organize neuronal intermediate filaments (neurofilaments or NFs) into three-dimensional networks by forming a steric “brush” around the NF core (Kumar et al., Biophysical Journal 2002). We recently engineered, expressed, and purified NF-inspired IDPs and showed that we could assemble these molecules into stimulus-responsive films. These films could be “shaved” to defined heights by proteolytically cleaving the brush at defined positions within the sequence (Srinivasan et al., Nature Communications 2014). We have also extended this approach to synthetic peptides (Bhagawati et al., Langmuir 2016).