Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus

For a chemical signal to propagate across a cell, it must navigate a tortuous environment involving a variety of organelle barriers. In this work we study mathematical models for a basic chemical signal, the arrival times at the nuclear membrane of proteins that are activated at the cell membrane an...

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Veröffentlicht in:PLoS computational biology 2020-11, Vol.16 (11), p.e1008356-e1008356
Hauptverfasser: Ma, Jingwei, Do, Myan, Le Gros, Mark A, Peskin, Charles S, Larabell, Carolyn A, Mori, Yoichiro, Isaacson, Samuel A
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container_issue 11
container_start_page e1008356
container_title PLoS computational biology
container_volume 16
creator Ma, Jingwei
Do, Myan
Le Gros, Mark A
Peskin, Charles S
Larabell, Carolyn A
Mori, Yoichiro
Isaacson, Samuel A
description For a chemical signal to propagate across a cell, it must navigate a tortuous environment involving a variety of organelle barriers. In this work we study mathematical models for a basic chemical signal, the arrival times at the nuclear membrane of proteins that are activated at the cell membrane and diffuse throughout the cytosol. Organelle surfaces within human B cells are reconstructed from soft X-ray tomographic images, and modeled as reflecting barriers to the molecules' diffusion. We show that signal inactivation sharpens signals, reducing variability in the arrival time at the nuclear membrane. Inactivation can also compensate for an observed slowdown in signal propagation induced by the presence of organelle barriers, leading to arrival times at the nuclear membrane that are comparable to models in which the cytosol is treated as an open, empty region. In the limit of strong signal inactivation this is achieved by filtering out molecules that traverse non-geodesic paths.
doi_str_mv 10.1371/journal.pcbi.1008356
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subjects Active Transport, Cell Nucleus
B-Lymphocytes - metabolism
B-Lymphocytes - ultrastructure
Biology and Life Sciences
Boundary conditions
Cartesian coordinates
Cell activation
Cell Membrane - metabolism
Cell Membrane - ultrastructure
Cell membranes
Cell Nucleus - metabolism
Cell Nucleus - ultrastructure
Cell surface
Cellular signal transduction
Chemical reactions
Computational Biology
Computer Simulation
Cubes
Cyclic AMP
Dirichlet problem
Engineering and Technology
Exact solutions
Finite element method
Humans
Imaging, Three-Dimensional
Inactivation
Intracellular signalling
Kinases
Kinetics
Lymphocytes
Lymphocytes T
Mathematical models
Mathematics
Medicine and Health Sciences
Membranes
Models, Biological
Nuclear Envelope - metabolism
Nuclear Envelope - ultrastructure
Observations
Organelles
Physiological aspects
Probability density functions
Propagation
Protein kinase
Proteins
Receptors
Representations
Robustness (mathematics)
Signal Transduction - physiology
Signaling
Statistics
Synaptogenesis
T cell receptors
T-cell receptor
Tomography
Tomography, X-Ray
title Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus
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