Hierarchical Prototissues With Structural and Functional Heterogeneity Enable Chemical‐Physical Communication‐Driven Diversified Movements

ABSTRACT Structural and functional heterogeneity is a defining feature of natural tissues, facilitating ordered integration of different tissue components through extracellular matrix (ECM) mediated intercellular communication and ultimately enabling responsive, collective movements. Nevertheless, the fabrication of functionally engineered, heterogeneous tissue‐mimicking materials capable of achieving intercellular communication‐assisted movements remains a major challenge in bottom‐up synthetic biology. Here, we co‐assemble enzyme‐ or magnetic nanoparticle‐encapsulated protocells into hierarchical prototissues with structural and functional heterogeneity using a modular, extra‐protocellular matrix (EPCM)‐assisted integration method. The prototissues exhibit enzyme‐powered buoyancy through the generation of oxygen by an inter‐protocellular glucose oxidase–catalase cascade reaction and the accumulation of oxygen bubbles within the matrix. In addition, the incorporation of magnetically responsive protocells endows the system with magnetically controllable motion. By orderly integrating chemical and physical responsive modules through EPCM, we achieve controlled underwater oscillation and shape change. Overall, our approach establishes heterogeneous functional prototissues with controllable motility and deformation capabilities, providing a model system for chemical‐physical stimulus‐responsive behaviors and spatial reconfiguration, and offering opportunities for bottom‐up synthetic biology and tissue engineering.