TY - JOUR
T1 - Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus
AU - Ma, Jingwei
AU - Do, Myan
AU - Le Gros, Mark A.
AU - Peskin, Charles S.
AU - Larabell, Carolyn A.
AU - Mori, Yoichiro
AU - Isaacson, Samuel A.
N1 - Publisher Copyright:
© 2020 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2020/11/16
Y1 - 2020/11/16
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pcbi.1008356
DO - 10.1371/journal.pcbi.1008356
M3 - Article
C2 - 33196636
AN - SCOPUS:85097003842
SN - 1553-734X
VL - 16
JO - PLoS computational biology
JF - PLoS computational biology
IS - 11
M1 - e1008356
ER -