Biomaterial design inspired by membraneless organelles

Membraneless organelles (MLOs) are phase-separated liquid com-partments providing spatiotemporal control of biomolecules and metabolism within cells. While MLOs exhibit intriguing properties, including efficient compositional regulation, thermodynamic meta-stability, environmental sensitivity, and reversibility, their formation is driven by weak non-covalent interactions derived from simple motifs of intrinsically disordered proteins (IDPs). Understanding the natural design of IDPs and the liquid-liquid phase-separation behavior will reveal insights about the contributions of MLOs to cellular physiology and disease and provide inspiration for the de novo design of dynamic biomolecule depots, self-regulated biochemical reactors, and stimulus-responsive systems. Here, the sequence and structural features of IDPs that contribute to the organization of MLOs are reviewed. Artificial MLOs formed following these principles, including self-assembling peptides, syn-thetic IDPs, polyelectrolytes, and peptide-polymer hybrids, are described. Finally, we illustrate the applications and discuss the po-tential application of MLO-inspired biomaterials, with examples spanning biochemical reactors, synthetic biology, drug discovery, and drug delivery.

Automated summary

Membraneless organelles (MLOs) are phase-separated liquid compartments in cells that provide precise control over biomolecules and metabolism. Their formation relies on weak non-covalent interactions of intrinsically disordered proteins (IDPs). Understanding the design and behavior of IDPs in liquid-liquid phase separation is crucial for understanding the contributions of MLOs to cellular physiology and disease. This knowledge can also inspire the design of biomaterials and systems in various fields.