  Liquid-liquid phase separation (LLPS) is an emerging and universal mechanism
for intracellular biomolecule organization, particularly, via the formation of
membraneless organelles (MOs). Intrinsically disordered proteins (IDPs) are the
main constituents of MOs, wherein multivalent interactions and low-complexity
domains (LCDs) drive LLPS. Using short oligopeptide derived from LCDs as
'stickers' and dextran backbones as 'spacers', we designed polymer-oligopeptide
hybrids to mimic the multivalent FUS protein as represented by the
'stickers-and-spacers' model. We demonstrated that hybrids underwent LLPS and
self-assembled into micron-sized (mostly 1-10 micron, resembling LLPS in vitro
and in living cells) compartments displaying liquid-like properties.
Furthermore, the droplets formed were capable of recruiting proteins and RNAs,
whilst providing a favorable environment for enhanced biochemical reaction,
thereby mimicking the function of natural MOs. We envision this simple yet
versatile model system will help elucidate the molecular interactions
implicated in MO formation and pave ways to a new type of biomimetic materials.
