Lipid network crosslinked hydrogels control material dynamics across multiple length scales through lipid movement

Control over network dynamics across length scales is a feature of natural materials challenging to replicate in synthetic hydrogels. Taking inspiration from biological materials that feature lipids as structural elements, we introduce Lipid Network Crosslinked (LINC) hydrogels that exploit the mobility of individual lipids within self-assembled liposomes as covalent, network-crosslinking points. These mobile, covalent crosslinks increase hydrogel stress relaxation rates over 20-fold compared to polymer-only hydrogels with equivalent stiffness. Liposome design parameters, including degree of surface functionalization and tail saturation, provide a means to independently control the macroscale storage moduli and stress relaxation behavior. Finally, we place cell-adhesive ligands onto more mobile or less mobile network elements. Human neural progenitor cells within LINC hydrogels significantly alter their phenotype in response to nanoscale ligand dynamics. These results establish LINC hydrogels as biomimetic materials that leverage nanoscale lipid mobility within a macroscale polymeric network to control dynamics at multiple length scales. Native tissues exhibit distinct dynamics across multiple length scales owing to their hierarchical network architecture. Replicating these behaviors in engineered materials remains challenging because macroscale viscoelasticity and nanoscale mobility are difficult to tune independently. Here, the authors develop a structural hydrogel in which self-assembled lipid nanostructures are covalently integrated into polymer networks, enabling independent control of viscoelasticity and nanoscale mobility.