bims-fascar Biomed News
on Phase separation and cellular architecture
Issue of 2019–05–19
three papers selected by
Victoria Yan, Max Planck Institute of Molecular Cell Biology and Genetics



  1. Elife. 2019 May 14. pii: e42315. [Epub ahead of print]8
      Liquid cellular compartments form in the cyto- or nucleoplasm and can regulate aberrant protein aggregation. Yet, the mechanisms by which these compartments affect protein aggregation remain unknown. Here, we combine kinetic theory of protein aggregation and liquid-liquid phase separation to study the spatial control of irreversible protein aggregation in the presence of liquid compartments. We find that even for weak interactions aggregates strongly partition into the liquid compartment. Aggregate partitioning is caused by a positive feedback mechanism of aggregate nucleation and growth driven by a flux maintaining the phase equilibrium between the compartment and its surrounding. Our model establishes a link between specific aggregating systems and the physical conditions maximizing aggregate partitioning into the compartment. The underlying mechanism of aggregate partitioning could be used to confine cytotoxic protein aggregates inside droplet-like compartments but may also represent a common mechanism to spatially control irreversible chemical reactions in general.
    Keywords:  none; phase separation; physics of living systems; protein aggregation; spatial regulation
    DOI:  https://doi.org/10.7554/eLife.42315
  2. Eur Phys J E Soft Matter. 2019 May 16. 42(5): 57
      We consider a continuum model for motility-induced phase separation (MIPS) of active Brownian particles (ABP) (J. Chem. Phys. 142, 224149 (2015)). Using a recently introduced perturbative analysis (Phys. Rev. E 98, 020604(R) (2018)), we show that this continuum model reduces to the classic Cahn-Hilliard (CH) model near the onset of MIPS. This makes MIPS another example of the so-called active phase separation. We further introduce a generalization of the perturbative analysis to the next higher order. This results in a generic higher-order extension of the CH model for active phase separation. Our analysis establishes the mathematical link between the basic mean-field ABP model on the one hand, and the leading order and extended CH models on the other hand. Comparing numerical simulations of the three models, we find that the leading-order CH model agrees nearly perfectly with the full continuum model near the onset of MIPS. We also give estimates of the control parameter beyond which the higher-order corrections become relevant and compare the extended CH model to recent phenomenological models.
    Keywords:  Soft Matter: Self-organisation and Supramolecular Assemblies
    DOI:  https://doi.org/10.1140/epje/i2019-11825-8
  3. Cell. 2019 May 07. pii: S0092-8674(19)30449-0. [Epub ahead of print]
      Segregation of maternal determinants within the oocyte constitutes the first step in embryo patterning. In zebrafish oocytes, extensive ooplasmic streaming leads to the segregation of ooplasm from yolk granules along the animal-vegetal axis of the oocyte. Here, we show that this process does not rely on cortical actin reorganization, as previously thought, but instead on a cell-cycle-dependent bulk actin polymerization wave traveling from the animal to the vegetal pole of the oocyte. This wave functions in segregation by both pulling ooplasm animally and pushing yolk granules vegetally. Using biophysical experimentation and theory, we show that ooplasm pulling is mediated by bulk actin network flows exerting friction forces on the ooplasm, while yolk granule pushing is achieved by a mechanism closely resembling actin comet formation on yolk granules. Our study defines a novel role of cell-cycle-controlled bulk actin polymerization waves in oocyte polarization via ooplasmic segregation.
    Keywords:  actin comets; actomyosin flows; ooplasmic streaming; phase segregation; zebrafish
    DOI:  https://doi.org/10.1016/j.cell.2019.04.030