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

Jingwei Ma, Myan Do, Mark A. Le Gros, Charles S. Peskin, Carolyn A. Larabell, Yoichiro Mori, Samuel A. Isaacson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere1008356
JournalPLoS computational biology
Volume16
Issue number11
DOIs
StatePublished - Nov 16 2020

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Ecology
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

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