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.