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

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