(540h) Modular Fusion Proteins and Surface-Enhanced Agar Hydrogels: A Versatile Platform for Facile Customization in Artificial Organelle Development

Organelles play a critical role in spatially segregating cellular activities which sustain life in eukaryotic cells. To gain deeper insights into complex cellular functions and exert control over them, researchers are actively pursuing the development of artificial organelles, making great progress towards biomimicry of complex cellular functions such as energy production, communication, and cytoskeletal development. However, the development of artificial organelles is often bottlenecked due to the need for complex compartmentalization strategies, which must be uniquely designed to mimic the specific functions of the targeted organelle. Here, we propose surface-enhanced agar hydrogel particles with modular fusion proteins as a versatile platform to simplify the development of artificial organelles. Agar, recognized for its biocompatibility, degradability, and tunable mechanical properties, offers significant potential for engineered biomimicry. Despite these advantageous properties, its application in artificial organelle development is still not fully exploited. We sought to demonstrate the versatility of agar hydrogel particles as an artificial organelle platform by leveraging the strong biofouling behavior of agar to alter physical and biochemical properties of the particle surfaces. Furthermore, by integrating them with modular fusion proteins, we showcase a range of biomimetic functions, such as reversible higher-order assembly and stimuli-responsiveness, in a cost-effective and straightforward manner. This work stands to accelerate the development of artificial organelles and nanomedicines with biomimetic functions through introducing a platform which is highly biocompatible, and easy to synthesize, modify, and degrade.