4.8 Review

Biomaterial design inspired by membraneless organelles

Journal

MATTER
Volume 5, Issue 9, Pages 2787-2812

Publisher

CELL PRESS
DOI: 10.1016/j.matt.2022.07.001

Keywords

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Funding

  1. Hong Kong Research Grants Council [GRF 16102520, GRF 16103517]
  2. Hong Kong PhD Fellowship Scheme

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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.
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.

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