A 3-D model of ligand transport in a deforming extracellular space

Nikola Kojić, Austin Huang, Euiheon Chung, Miloš Ivanović, Nenad Filipović, Miloš Kojić, Daniel J. Tschumperlin

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Cells communicate through shed or secreted ligands that traffic through the interstitium. Force-induced changes in interstitial geometry can initiate mechanotransduction responses through changes in local ligand concentrations. To gain insight into the temporal and spatial evolution of such mechanotransduction responses, we developed a 3-D computational model that couples geometric changes observed in the lateral intercellular space (LIS) of mechanically loaded airway epithelial cells to the diffusion-convection equations that govern ligand transport. By solving the 3-D fluid field under changing boundary geometries, and then coupling the fluid velocities to the ligand transport equations, we calculated the temporal changes in the 3-D ligand concentration field. Our results illustrate the steady-state heterogeneities in ligand distribution that arise from local variations in interstitial geometry, and demonstrate that highly localized changes in ligand concentration can be induced by mechanical loading, depending on both local deformations and ligand convection effects. The occurrence of inhomogeneities at steady state and in response to mechanical loading suggest that local variations in ligand concentration may have important effects on cell-to-cell variations in basal signaling state and localized mechanotransduction responses.

Original languageEnglish (US)
Pages (from-to)3517-3525
Number of pages9
JournalBiophysical Journal
Volume99
Issue number11
DOIs
StatePublished - Dec 1 2010

ASJC Scopus subject areas

  • Biophysics

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    Kojić, N., Huang, A., Chung, E., Ivanović, M., Filipović, N., Kojić, M., & Tschumperlin, D. J. (2010). A 3-D model of ligand transport in a deforming extracellular space. Biophysical Journal, 99(11), 3517-3525. https://doi.org/10.1016/j.bpj.2010.09.044