Stiff, Multistimuli-Responsive Supramolecular Hydrogels as Unique Molds for 2D/3D Microarchitectures of Live Cells

Supramolecular hydrogels constructed through molecular self-assembly of small molecules have unique stimuli-responsive properties; however, they are mechanically weak in general, relative to conventional polymer gels. Very recently, we developed a zwitterionic amino acid tethered amphiphilic molecule 1, which gave rise to a remarkably stiff hydrogel comparable with polymer-based agarose gel, retaining reversible thermal-responsive properties. In this study, we describe that rational accumulation of multiple and orthogonal noncovalent interactions in the supramolecular nanofibers of 1 played crucial roles not only in the mechanical reinforcement but also in the multistimuli responsiveness. That is, the zwitterionic amino acid moiety and the C-C double bond unit of the hydrogelator 1 can function as a pH-responsive unit and a light-responsive unit, respectively. We also demonstrated that this stiff and multistimuli-responsive supra-molecular hydrogel 1 is applied as a unique mold for 2D and 3D-patterning of various substances. More significantly, we succeeded in the fabrication of a collagen gel for spatial patterning, culturing, and differentiation of live cells by using hydrogel 1 molds equipped with 2D/3D microspace channels (100-200 mm in diameter).