A cell size threshold limits cell polarity and asymmetric division potential

Area of Science:

• Cell biology
• Developmental biology
• Systems biology

Background:

• Reaction-diffusion networks are crucial for pattern formation in biological systems, including cell polarization.
• Scaling of molecular network outputs with system size is essential for biological processes.
• The kinetic properties of molecules can limit a network's ability to adapt to changes in size.

Purpose of the Study:

• To investigate the constraints on size scaling within the conserved PAR cell polarity network.
• To determine the consequences of this lack of scaling in the C. elegans germ lineage.
• To explore the relationship between cell size, polarity, and cell division asymmetry.

Main Methods:

• Utilized the C. elegans embryo germ lineage as a model system.
• Performed theoretical analysis of the PAR protein network's behavior.
• Developed empirically-constrained models to simulate network dynamics.
• Conducted experiments involving genetic and physical reduction of germ lineage cell size.

Main Results:

• The behavior of PAR proteins in the C. elegans germ lineage does not scale with cell size.
• A theoretical size threshold was identified below which cell polarity is destabilized, leading to an unpolarized state.
• This destabilization threshold correlates with the normal switch between asymmetric and symmetric cell division modes.
• Reducing cell size experimentally triggered loss of polarity at predicted thresholds.

Conclusions:

• Physical limitations in polarity networks prevent scaling with cell size, leading to a size-dependent polarity threshold.
• This size threshold influences cell division asymmetry and potentially cell fate decisions.
• Cells may use physical limits of polarity networks to interpret geometrical cues for fate determination.