The Effect of Noisy Flow on Endothelial Cell Mechanotransduction: A Computational Study

Abstract

Flow in the arterial system is mostly laminar, but turbulence occurs in vivo under both normal and pathological conditions. Turbulent and laminar flow elicit significantly different responses in endothelial cells (ECs), but the mechanisms allowing ECs to distinguish between these different flow regimes remain unknown. The authors present a computational model that describes the effect of turbulence on mechanical force transmission within ECs. Because turbulent flow is inherently “noisy” with random fluctuations in pressure and velocity, our model focuses on the effect of signal noise (a stochastically changing force) on the deformation of intracellular transduction sites including the nucleus, cell–cell adhesion proteins (CCAPs), and focal adhesion sites (FAS). The authors represent these components of the mechanical signaling pathway as linear viscoelastic structures (Kelvin bodies) connected to the cell surface via cytoskeletal elements. The authors demonstrate that FAS are more sensitive to signal noise than the nucleus or CCAP. The relative sensitivity of these various structures to noise is affected by the nature of the cytoskeletal connections within the cell. Finally, changes in the compliance of the nucleus dramatically affect nuclear sensitivity to noise, suggesting that pathologies that alter nuclear mechanical properties will be associated with abnormal EC responsiveness to turbulent flow.