RT Journal Article
SR Electronic
T1 Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.16.909333
DO 10.1101/2020.01.16.909333
A1 Jingwei Ma
A1 Myan Do
A1 Mark A. Le Gros
A1 Charles S. Peskin
A1 Carolyn A. Larabell
A1 Yoichiro Mori
A1 Samuel A. Isaacson
YR 2020
UL http://biorxiv.org/content/early/2020/01/17/2020.01.16.909333.abstract
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.