A 3-D Model of Ligand Transport in a Deforming Extracellular Space

• Published in: Biophysical journal Vol. 99; no. 11; pp. 3517 - 3525
• Main Authors: Kojić, Nikola, Huang, Austin, Chung, Euiheon, Ivanović, Miloš, Filipović, Nenad, Kojić, Miloš, Tschumperlin, Daniel J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2010; Biophysical Society; The Biophysical Society
• Subjects: ABC transporters; Biological Systems and Multicellular Dynamics; Biological Transport; Cells; Computational fluid dynamics; Diffusion; Extracellular Space - metabolism; Flow velocity; Fluid flow; Fluids; Geometry; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Interstitials; Ligands; Load; Mathematical models; Models, Biological; Molecules; Rheology; Signal transduction; Temporal logic; Transport
• ISSN: 0006-3495; 1542-0086
• DOI: 10.1016/j.bpj.2010.09.044

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.