Phototunable Viscoelasticity in Hydrogels Through Thioester Exchange

The extracellular matrix in which cells reside offers elastic and viscoelastic mechanical cues important for directing cell behavior. Recently, cellular responses to viscoelastic and elastic mechanical cues have been studied; however, questions remain as to how cells identify and transduce these cues differently, sparking a need for materials that can interrogate these properties separately. We present a cell culture substrate based on thioester exchange chemistry where viscoelasticity of the biophysical environment can be modulated in situ with light and the photoinitiated thiol-ene ‘click’ reaction. With this method, stress relaxation in thioester hydrogels with relaxation times ranging from 200,000-1,500,000s can be switched off in the presence of cells without change to the elastic modulus. NIH 3T3 fibroblasts cultured for 48 hr on viscoelastic substrates that transition to elastic substrates after 24 hr display cell morphology and YAP/TAZ expression similar to the elastic control. Phototunable viscoelastic thioester hydrogels provide a tunable materials system to investigate time-dependent cellular responses to viscoelasticity and should prove useful for understanding the dynamics of mechanoresponsive cellular pathways.