Dynamic modeling for flow-activated chloride-selective membrane current in vascular endothelial cells

Abstract

In this paper, a dynamic model is proposed to quantify the relationship between fluid flow and Cl(-)-selective membrane current in vascular endothelial cells (VECs). It is assumed that the external shear stress would first induce channel deformation in VECs. This deformation could activate the Cl(-) channels on the membrane, thus allowing Cl(-) transport across the membrane. A modified Hodgkin-Huxley model is embedded into our dynamic system to describe the electrophysiological properties of the membrane, such as the Cl(-)-selective membrane current (I), voltage (V) and conductance. Three flow patterns, i. e., steady flow, oscillatory flow, and pulsatile flow, are applied in our simulation studies. When the extracellular Cl(-) concentration is constant, the I-V characteristics predicted by our dynamic model shows strong consistency with the experimental observations. It is also interesting to note that the Cl(-) currents under different flow patterns show some differences, indicating that VECs distinguish among and respond differently to different types of flows. When the extracellular Cl(-) concentration keeps constant or varies slowly with time (i.e. oscillates at 0.02 Hz), the convection and diffusion of Cl(-) in extracellular space can be ignored and the Cl(-) current is well captured by the modified Hodgkin-Huxley model alone. However, when the extracellular Cl(-) varies fast (i.e., oscillates at 0.2 Hz), the convection and diffusion effect should be considered because the Cl(-) current dynamics is different from the case where the convection-diffusion effect is simply ignored. The proposed dynamic model along with the simulation results could not only provide more insights into the flow-regulated electrophysiological behavior of the cell membrane but also help to reveal new findings in the electrophysiological experimental investigations of VECs in response to dynamic flow and biochemical stimuli.

Transport of Dynamic Biochemical Signals in Steady Flow in a Shallow Y-Shaped Microfluidic Channel: Effect of Transverse Diffusion and Longitudinal Dispersion

“…In recent years, the interactions between cells and extracellular microenvironments have received more attention in the field of cell biology [4][5][6][7][8]. Researches show that cells in response to dynamic signals exhibit different characteristics from those to static ones [9][10][11][12][13][14]. However, while most of the previous investigations focused on the cellular behaviors in response to static biomechanical and/or biochemical signals [9][10][11], few studied the effect of dynamic signals [12][13][14].…”

“…Researches show that cells in response to dynamic signals exhibit different characteristics from those to static ones [9][10][11][12][13][14]. However, while most of the previous investigations focused on the cellular behaviors in response to static biomechanical and/or biochemical signals [9][10][11], few studied the effect of dynamic signals [12][13][14]. Thus, a controlled quantitative loading of dynamic biomechanical and biochemical signals on cells cultured in vitro is needed to provide more insights into the biological processes and behaviors of the cells.…”

Fluid shear stress enhances the cell volume decrease of osteoblast cells by increasing the expression of the ClC-3 chloride channel

“…Various in vitro loading techniques, such as cell swelling, substrate stretch loading and fluid shear stress (FSS), are used in the study of osteocyte response to mechanical stimulation. However, the majority of studies do not recapitulate osteoblast anabolism under mechanical stimulation, including the activation of intracellular chloride ions, chloride channel genes and channel proteins (3)(4)(5)(6)(7). In fact, studies have shown that numerous ion channels [such as Ca 2+ channels (8) and K + channels (9)] have a role in osteogenic differentiation.…”

Oscillatory Flow Accelerates Autocrine Signaling due to Nonlinear Effect of Convection on Receptor-Related Actions

“…Theoretical studies focusing on the effects of oscillatory flow on cell cultures are rather rare. Qin et al (39) developed a mathematical model to investigate the interaction of the pulsatile and oscillatory flows with endothelial cells, especially the impacts of various flow regimes on the chloride transmembrane transport and the corresponding electric current. They showed that the endothelial cell can distinguish between the flow types by different electric current responses.…”