Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes.

@article{Wehrens2014PositiveFC,
  title={Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes.},
  author={Martijn Wehrens and Pieter Rein ten Wolde and Andrew Mugler},
  journal={The Journal of chemical physics},
  year={2014},
  volume={141 20},
  pages={
          205102
        }
}
Clustering of molecules on biological membranes is a widely observed phenomenon. A key example is the clustering of the oncoprotein Ras, which is known to be important for signal transduction in mammalian cells. Yet, the mechanism by which Ras clusters form and are maintained remains unclear. Recently, it has been discovered that activated Ras promotes further Ras activation. Here we show using particle-based simulation that this positive feedback is sufficient to produce persistent clusters of… 

Figures from this paper

Nonequilibrium biochemical structures in two space dimensions with local activation and regulation.
TLDR
It is shown that coherent clustering can lead to digital signaling and receptor competition in biochemical systems where the model gives a recruitment mechanism for the reinforcement of the mechanical linkage with the extracellular matrix.
Confinement and diffusion modulate bistability and stochastic switching in a reaction network with positive feedback.
TLDR
It is shown that stochastic switching to a state maintained by positive feedback occurs by cluster formation and growth, and the frequency at which switching occurs depends nontrivially on the diffusion coefficient, which can promote or suppress switching relative to the well-mixed limit.
Spatiotemporal Effects of Transport and Network Topology in Biological Systems
TLDR
Stochastic simulation methods are applied to characterize the spatiotemporal behavior of three distinct biological systems and find that confined systems with high molecular mobility promote the active steady state, and stochastic switching occurs unidirectionally by nucleation and growth of single active clusters.
Particle-based simulations of polarity establishment reveal stochastic promotion of Turing pattern formation
TLDR
This work represents the first particle-based simulations of a model for yeast polarization that is based on a Turing mechanism, and finds that stochastic fluctuations speed polarity establishment and permit polarization in parameter regions predicted to be Turing stable.
Multi-scale simulation of reaction-diffusion systems
In many reaction-diffusion processes, ranging from biochemical networks, catalysis, to complex self-assembly, the spatial distribution of the reactants and the stochastic character of their
Spatial-Stochastic Simulation of Reaction-Diffusion Systems
TLDR
EGFRD, a computationally efficient particle-based algorithm that makes use of analytical functions to accurately sample interparticle reactions and diffusive motion with large jumps in time and space, is focused on.
Stochastic Turing patterns in a synthetic bacterial population
TLDR
Genetically engineered bacterial populations with signaling molecules that form a stochastic activator–inhibitor system that does not satisfy the classic Turing conditions but exhibits disordered patterns with a defined length scale and spatial correlations that agree quantitatively with stochastically Turing theory.
Multiscale simulations of anisotropic particles combining molecular dynamics and Green's function reaction dynamics.
TLDR
This work presents the novel algorithm focusing on Brownian dynamics only, although the methodology is generic, and will open up the possibility for large scale simulations of protein signalling networks.
eGFRD in all dimensions.
TLDR
A new eGFRD version that implements the principle of eG FRD in all dimensions, thus enabling efficient particle-based simulation of biochemical reaction-diffusion processes in the 3D cytoplasm, on 2D planes representing membranes, and on 1D elongated cylinders representative of, e.g., cytoskeletal tracks or DNA.
...
...

References

SHOWING 1-10 OF 79 REFERENCES
Positive feedback regulation results in spatial clustering and fast spreading of active signaling molecules on a cell membrane.
TLDR
It is found that positive feedback, in the presence of slow diffusion, results in clustering of activated molecules on the plasma membrane, and rapid spatial spreading as the front of the cluster propagates with a constant velocity (dependent on the feedback strength).
A Density-Dependent Switch Drives Stochastic Clustering and Polarization of Signaling Molecules
TLDR
Regulating the density of signaling molecules provides a simple mechanism for a positive feedback circuit to robustly switch between clustered and un-clustered states, suggesting that finite sizes of molecular populations cannot be ignored in signal transduction networks.
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.
Spatial partitioning improves the reliability of biochemical signaling
TLDR
It is demonstrated that partitioning improves the reliability of biochemical signaling and suggests that molecular partitioning is not merely a consequence of the complexity of cellular substructures, but also plays an important functional role in cell signaling.
Direct visualization of Ras proteins in spatially distinct cell surface microdomains
TLDR
It is found that an inner-plasma membrane lipid raft marker displays cholesterol-dependent clustering in microdomains with a mean diameter of 44 nm that occupy 35% of the cell surface, illustrating that the inner plasma membrane comprises a complex mosaic of discrete micro domains.
Spatio-temporal correlations can drastically change the response of a MAPK pathway
TLDR
It is argued that slow ADP release by the enzymes can protect the system against these rapid rebindings of the enzyme molecules to the substrate molecules after modification of the first site, thus enabling ultrasensitivity and bistability.
Spatial organization in bacterial chemotaxis
TLDR
Assembly of receptor clusters appears to be a stochastic process, but bacteria evolved mechanisms to ensure optimal cluster distribution along the cell body for partitioning to daughter cells at division.
...
...