Glossary
Free energy: In a thermodynamic system, the portion of energy available to perform work at constant temperature. Specifically, the Gibbs free energy is used for constant temperature and pressure, which is true for solution-phase chemistry including biochemistry. Systems tend to transit into a state where the free energy is lower, which is more thermodynamically stable.
Intrinsically disordered proteins (IDPs) : The most common scaffold proteins of MLOs with a strong tendency to form LLPS, which is often concomitant with nucleic acids.
Kinked β sheets: The β-sheet with kinks that prevent side chains from tight interdigitating across the interface. Compared with the steric zipper structure in amyloid plaques, they interact weakly through polar atoms and aromatic side chains, bury smaller surface areas, and have lower binding energy.
Liquid-liquid phase separation (LLPS): A homogenous liquid phase demixes into two distinct liquid phases, namely, one light phase and one concentrated phase. This term is also widely referred as ‘coacervation’ when comprising macromolecular components.
Low complexity domains (LCDs) : Domains of IDPs with low sequence complexity and biased composition of amino acids, namely, typically enriched in specific polar and charged amino acids, whilst interspersed with aromatic residues (especially tyrosine and phenylalanine). They are also referred as ‘prion-like domains (PLDs)’, which is often considered as necessary and sufficient for driving LLPS of IDPs intracellularly.
Maturation: A transition process of MLOs from liquid-like droplets to solid-like aggregates, together with the loss of metastability. This process is thermodynamically spontaneous, which can take place simply over time or be accelerated by pathological changes. This term has also been referred to as ‘hardening’, ‘aging’ or ‘solidification’.
Membraneless organelles (MLOs) : Non-membrane-bound organelles that usually form via liquid-liquid phase separation in cells. They have also been referred to as many other names including biomolecular condensates, cellular bodies, speckles, puncta and granules.
Metastability /Metastable: A system is thermodynamically metastable when staying at a local minimum of free energy, with a tendency to spontaneously transit into more stable state, namely, a global minimum of free energy. The metastable nature of a thermodynamic system is metastability.
Neurodegenerative diseases : A group of diseases engendered by the progressive loss of structure and function of neurons, which is also known as degenerative nerve diseases. Common examples include Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease, Huntington’s disease, multiple system atrophy and frontotemporal dementia.
Steric zipper: The dry and tightly self-complementing structure formed within double β-sheets of amyloid-like fibrils. This name was coined by David Eisenberg’s group in 2005 because the interdigitating side chains of β-sheets resemble the teeth of a zipper.
Supersaturated: A protein is supersaturated when its concentration is higher than the solubility under normal conditions.