Computational modeling of extracellular mechanotransduction

Biophysical Journal
Nikola KojicDaniel J Tschumperlin

Abstract

Mechanotransduction may occur through numerous mechanisms, including potentially through autocrine signaling in a dynamically changing extracellular space. We developed a computational model to analyze how alterations in the geometry of an epithelial lateral intercellular space (LIS) affect the concentrations of constitutively shed ligands inside and below the LIS. The model employs the finite element method to solve for the concentration of ligands based on the governing ligand diffusion-convection equations inside and outside of the LIS, and assumes idealized parallel plate geometry and an impermeable tight junction at the apical surface. Using the model, we examined the temporal relationship between geometric changes and ligand concentration, and the dependence of this relationship on system characteristics such as ligand diffusivity, shedding rate, and rate of deformation. Our results reveal how the kinetics of mechanical deformation can be translated into varying rates of ligand accumulation, a potentially important mechanism for cellular discrimination of varying rate-mechanical processes. Furthermore, our results demonstrate that rapid changes in LIS geometry can transiently increase ligand concentrations in underlying m...Continue Reading

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Citations

Jan 9, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nikola KojicDaniel J Tschumperlin
Dec 18, 2010·Revue des maladies respiratoires·J MerrienP Chanez
Oct 7, 2009·Journal of Biomechanics·Daniel J TschumperlinFei Liu
Jun 22, 2015·Computers in Biology and Medicine·Nikola KojićMehmet Toner
Nov 30, 2010·Biophysical Journal·Nikola KojićDaniel J Tschumperlin
Jul 3, 2015·Physiology·Jin-Ah ParkJeffrey M Drazen
Jul 24, 2012·Soft Matter·Nikola KojicDavid L Kaplan
Feb 1, 2019·Journal of Engineering and Science in Medical Diagnostics and Therapy·Michael J O'Sullivan, Bo Lan
May 13, 2008·Journal of Theoretical Biology·Jens H KroegerMartin Grant

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