Endothelial cells and blood flow: a mathematical model of early mechanical and electrophysiological reponses to shear stress
Graduation Date
2011
Document Type
Thesis
Program
Other
Program
Thesis (M.S.)--Humboldt State University, Environmental Systems: Mathematical Modeling, 2011
Committee Chair Name
Borbala Mazzag
Committee Chair Affiliation
HSU Faculty or Staff
Keywords
Humboldt State University -- Theses -- Mathematical Modeling, Blood flow, Endothelial cells, Mathematical modeling
Abstract
Atherosclerosis, hardening of the arteries, is a leading cause of death in America. Endothelial cells line the arteries and exhibit different morphology (shape) and different physiological properties in areas where atherosclerosis tends to develop. A better understanding of endothelial cell behavior will lead to a better understanding of this disease. This thesis outlines a model of early mechanical and electrophysiological responses following the onset of or change in blood flow. The model describes deformation of actin filaments and the cellular membrane under different blood flow conditions. We hypothesize that Kir ion channels are activated by the actin filament deformations and Cl– ion channels are activated by the membrane deformations. The deformations activate the channels by changing channel conductance. The sensitivity of these channels to different blood flow conditions allow them to act as flow sensors. Activation of the ion channels initiates biochemical signaling involving Ca²+, IP[subscript 3], K+, CL–, and Na+ with the changing ion concentrations leading to fluctuation of the membrane potential. We tested our model against experimentally observed Kir and Cl– currents, cytosolic calcium concentration, and membrane potentials measured before, during, on after the onset of flow. Our model failed to capture the cellular behavior observed in experiment, but it may serve as the basis of improved models of the coupling of mechanical and electrophysiological signals in ECs.
Recommended Citation
Pace, Jonathan R., "Endothelial cells and blood flow: a mathematical model of early mechanical and electrophysiological reponses to shear stress" (2011). Cal Poly Humboldt theses and projects. 1729.
https://digitalcommons.humboldt.edu/etd/1729
https://scholarworks.calstate.edu/concern/theses/g445cg689