A designer minimalistic model parallels the phase-separation-mediated assembly and biophysical cues of extracellular...

The propensity for controlled liquid-liquid phase separation and subsequent directed phase transition are crucial for the coacervation-mediated assembly of extracellular matrix (ECM). This spatiotemporally controlled ECM assembly can be used to develop coacervate-based polymer assembly strategies to generate biomimetic materials that can emulate the complex structures and biophysical cues of the ECM. Inspired by the tropoelastin structure, here we develop a designer minimalistic model consisting of alternating hydrophobic moieties and covalent crosslinking domains. By increasing the valence and enhancing the interaction strength of the hydrophobic moieties, we can control the degree of the assembly to enhance the propensity for phase separation and thus emulate the extracellular coacervation process of tropoelastin, including droplet formation, coalescence and maturation. The subsequent covalent-bonding-triggered coacervate-hydrogel transition with enhanced assembly order stabilizes the phase-separated structure in the form of a heterogeneous hydrogel, thereby mimicking covalent crosslinking-derived elastin fibrillation. Furthermore, the heterogeneous hydrogel network establishes a biomimetic matrix that can effectively promote the mechanosensing of adherent stem cells.