Collagen imparts structure, viscoelasticity, and bioactivity to the extracellular matrix (ECM) with variance between organs and between healthy and diseased states. Synthetic mimics of collagen-rich tissues remain a need in applications, from biological studies to regenerative medicine, for parsing and controlling these properties. We designed multifunctional collagen mimetic peptides (mfCMPs) that self-assemble into triple helices and fibrils and contain integrin binding motifs: GFOGER, a binding site within intact collagen I, and RGD, a cryptic binding site available within denatured collagen I. These mfCMPs are incorporated into hydrogel-based synthetic ECMs to impart collagen-like hierarchical structures, viscoelasticity, and bioactivity with modularity. We establish innovative methods for imaging the resulting nano- and micro-structures within the hydrogel using super-resolution microscopy. The physically assembled mfCMPs impart tunable, concentration-dependent viscoelasticity within otherwise elastic, covalently cross-linked hydrogels, exhibiting relaxation half times over orders of magnitude and similar to soft tissues. Notably, breast cancer cells encapsulated and cultured in synthetic ECMs with a bioactive fibrillar structure and viscoelastic properties formed large, growing spheroids. Overall, these modular building blocks provide an innovative tool for creating fully synthetic surrogates of collagen-rich microenvironments, aiding both fundamental and translational biological studies and providing a framework to imbue tunable viscoelasticity to synthetic ECMs.
Castro et al. (Sat,) studied this question.