Biomaterial design inspired by membraneless organelles

Membraneless organelles (MLOs) are phase-separated liquid compartments providing spatiotemporal control of biomolecules and metabolism within cells. While MLOs exhibit intriguing properties, including efficient compositional regulation, thermodynamic metastability, 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, synthetic IDPs, polyelectrolytes, and peptide-polymer hybrids, are described. Finally, we illustrate the applications and discuss the potential application of MLO-inspired biomaterials, with examples spanning biochemical reactors, synthetic biology, drug discovery, and drug delivery.