Cell Polarity: Quantitative Modeling as a Tool in Cell Biology

@article{Mogilner2012CellPQ,
  title={Cell Polarity: Quantitative Modeling as a Tool in Cell Biology},
  author={Alex Mogilner and Jun Allard and Roy Wollman},
  journal={Science},
  year={2012},
  volume={336},
  pages={175 - 179}
}
Among a number of innovative approaches that have modernized cell biology, modeling has a prominent yet unusual place. One popular view is that we progress linearly, from conceptual to ever more detailed models. We review recent discoveries of cell polarity mechanisms, in which modeling played an important role, to demonstrate that the experiment-theory feedback loop requires diverse models characterized by varying levels of biological detail and mathematical complexity. We argue that a… 

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References

SHOWING 1-10 OF 76 REFERENCES

A Comparison of Mathematical Models for Polarization of Single Eukaryotic Cells in Response to Guided Cues

TLDR
It is found that the diversity of cell behaviors is reflected by a diversity of models, and that some, but not all models, can account for amplification of stimulus, maintenance of polarity, adaptation, sensitivity to new signals, and robustness.

Adaptation of core mechanisms to generate cell polarity

TLDR
Analysis of evolutionarily diverse cell types reveals that cell-surface landmarks adapt core pathways for cytoskeleton assembly and protein transport to generate cell polarity.

Modular coherence of protein dynamics in yeast cell polarity system

TLDR
A simple model is proposed that approximates a PCD protein's molecular residence time as the sum of the characteristic time constants of the functional modules with which it interacts, weighted by the number of edges forming these interactions.

On the spontaneous emergence of cell polarity

TLDR
This work identifies an intrinsic stochastic mechanism through which positive feedback alone is sufficient to account for the spontaneous establishment of a single site of polarity, and finds that the polarization frequency has an inverse dependence on the number of signalling molecules: the frequency of polarization decreases as theNumber of molecules becomes large.

Model of polarization and bistability of cell fragments.

TLDR
A purely thermodynamic (not involving signaling) quantitative model of the cell polarization and bistability is suggested based on observations of lamellipodial fragments of fish keratocyte cells and generates quantitative predictions about relations between the intracellular forces' magnitudes and the cell geometry and motility.

Physical model of cellular symmetry breaking.

TLDR
In this article, it is discussed how simplified model systems can help to understand the physics that underlie the mechanics of symmetry breaking.

Spontaneous Cell Polarization Through Actomyosin-Based Delivery of the Cdc42 GTPase

TLDR
An assay in yeast where expression of an activated form of Cdc42, a Rho-type guanosine triphosphatase (GTPase) required for cell polarization, could generate cell polarity without any recourse to a preestablished physical cue was used.
...