PT  - JOURNAL ARTICLE
AU  - Jingwei Ma
AU  - Myan Do
AU  - Mark. A. Le Gros
AU  - Charles S. Peskin
AU  - Carolyn A. Larabell
AU  - Yoichiro Mori
AU  - Samuel A. Isaacson
TI  - Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus
AID  - 10.1101/2020.01.16.909333
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.16.909333
4099  - http://biorxiv.org/content/early/2020/08/12/2020.01.16.909333.short
4100  - http://biorxiv.org/content/early/2020/08/12/2020.01.16.909333.full
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.Competing Interest StatementThe authors have declared no competing interest.