12.2018 | THE SCIENTIST 33Nucleolus
Nucleus
MembranelessCytoplasmorganelleProtein
chainsInteractions
between protein
chainsSolventDNA double helixDNA Ddx4Absorbed
into organelleExcluded
from organelleSingle-
strandedMembraneless
organelle interiorDdx4 proteins in model membraneless
organelles split the DNA double helix
into single strands.Tau protein
chainsPhase-separated
dropletPathological
aggregate© KIMBERLY BATTISTA
Alongside organelles such as mitochondria and Golgi apparatuses, membraneless structures help compartmentalize the cytoplasm, as well
as the interior of the nucleus. In contrast to organelles with a lipid bilayer membrane, membraneless structures are formed through a process
known as liquid-liquid phase separation. When it comes to how and why cells create and use membraneless organelles, however, there are still
more questions than answers.NAKED ORGANELLES
»MEMBRANELESS
ORGANELLE ACCESS
In addition to the primary polymers that make up
the membraneless organelle, small molecules, proteins,
and nucleic acids can potentially enter the structure.
Whether or not a particular molecule will be absorbed
or excluded depends on how it interacts with the
interior and exterior environments.»MEMBRANELESS ORGANELLE FORMATION
For liquid-liquid phase separation to occur in cells, the polymers that make up
membraneless organelles—typically highly flexible proteins and nucleic acids—
must exceed what is called their saturation concentration, or ”solubility limit,”
in the cytoplasm or nucleoplasm. Below this level, the polymer chains dissolve
into the surrounding cellular solution; if the saturation concentration is exceeded,
the extra polymer chains condense into liquid-like droplets. The polymer chains
inside and outside the droplets are therefore in equilibrium, meaning they contin-
uously escape and rejoin the membraneless organelle.MEMBRANELESS ORGANELLE
EMERGENT PROPERTIES
Although researchers have much to learn
about what happens to molecules that enter
the organelle environment, one example—the
passive unwinding of nucleic acids—has been
demonstrated in vitro in model membrane-
less structures made up of one or a few
protein types.»LIQUID-LIQUID PHASE SEPARATION IN DISEASE
The aggregation of proteins is characteristic of several neurodegenerative diseases,
and liquid dynamics within the cell may support this pathological activity. For example,
the tau protein that makes up neurofibrillary tangles characteristic of Alzheimer’s
disease appears to form phase-separated liquid droplets in neurons before developing
into tau aggregates.»