On how C. elegans spatially segregates Non-Membrane

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On how C. elegans spatially segregates Non-Membrane-Bound
Compartments
Christoph A. Weber
Max Planck Institute for the Physics of Complex Systems, Division of Biological Physics
P granules are cytoplasmic RNA/protein condensates known to determine the germ lineage
in Caenorhabditis elegans. They resemble striking similarities with liquid droplets, such as
dripping, shearing and wetting. Assuming that P granules are liquid-like we consider how
they form in the crowded cytoplasm and how P granules are spatially segregated to one side of
the cell.
First P granule formation in-vivo and in-vitro are
shown to share all hallmarks with a liquid-liquid phase-separation. Specifically, demixing in-vivo
is determined by temperature and concentration and the droplet formation is reversible with
respect to temperature quenches. The finding that P granules are formed by liquid-liquid
demixing breaks
the paradigmatic view that a molecular machinery is necessary to build up organelles through
complex biological pathways. Liquid-liquid demixing could also serve as a mechanism for the
assembly of non-membrane-bound compartments in other living organisms.
Based on the insight that P granules can be regarded as liquid-like protein droplets we propose
an extended Flory-Huggins model to describe the dynamics of P granule growth, interaction
and spatial regulation. Specifically, guided by recent experimental observations we
consider that PGL-3 competes with Mex-5 about mRNA and show that this mechanism is
sufficient to explain
that P granules only form at the side of the cell where the Mex-5 level is low.
From the model we can compute quantitatively the gradient of supersaturation and study the
ripening dynamics
of the protein droplets.
We find that ripening in a gradient is significantly accelerated making it to a rather efficient
mechanism of concentrating material locally.
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