The relationship between ECM mechanics and cell behavior is dynamic, as cells remodel and respond to changes in their local environment. Most in vitro substrates are static and supraphysiologically stiff; thus, platforms with dynamic and reversible mechanical changes are needed. Here, we developed hyaluronic acid-based substrates capable of sequential photodegradation and photoinitiated crosslinking reactions to soften and then stiffen the hydrogels over a physiologically-relevant range of moduli. Reversible mechanical signaling to adhered cells was demonstrated with human mesenchymal stem cells. In situ hydrogel softening (from ~14 to 3.5 kPa) led to a decrease in cell area and nuclear localization of YAP/TAZ, and subsequent stiffening (from ~3.5 to 28 kPa) increased cell area and nuclear localization of YAP/TAZ. Each photoreaction was cytocompatible and tunable, rendering this platform amenable to studies of dynamic mechanics on cell behavior across many cell types and contexts.
Citation: Angewandte Chemie-International Edition
Pub Type: Journals
Hydrogels, ECM Mechanics, Atomic Force Microscopy