Crosstalk between Shear Stress and Human Brain Microvascular Endothelial Cells

Sungkwon Kang1

Advisors: Yong Woo Lee2, Pavlos P. Vlachos1,2

1Department of Mechanical Engineering and 2School of Biomedical Engineering and Sciences, Virginia Tech

Blood flow in human circulatory system exclusively interacts with endothelial cells that cover the inside of blood vessels. The interactions are not only induced by chemical signals flowing in bloodstream but also shear stresses generated on wavy surface of endothelial cells by blood flow.

Introduction

It remains unknown whether change in properties of endothelial cells can alter the profile of the blood flow. In the present study, we hypothesized that morphological change in diseased endothelial cells could induce a flow disturbance which would act as physical stimuli to affect neighboring cells.

Hypothesis

Particle Image Velocimetry and Flow Chamber Experiment

Velocity profile of water flow in the chamber was successfully retrieved as well as the wall shear stress exerted on glass slides without endothelial cells seeded. Particle Image Velocimetry (PIV) provides

instantaneous velocity vector measurements in a cross-section of a flow. The velocity vectors are derived from sections of the target area of the particle-seeded flow by measuring the movement of particles between two light pulses.

Observing the influence of the endothelial cells to the fluid flow within the flow channel will enhance the understanding whether the endothelial cells have the ability to manipulate the blood flow.

AcknowledgementsI would like to acknowledge my advisors, Dr. Yong Woo

Lee, and Dr. Pavlos P. Vlachos, as well as Ph.D. candidate, Ali Etebari.

Figure 1. Endothelial cells in culture and cross-sectional view of true capillary

Figure 7. Active ionic polymer schematic and a prototype ionic polymer wall shear sensor

Figure 4. Particle Image Velocimetry and flow chamber apparatus, flow chamber schematic design and the actual flow chamber (clockwise from the left)

Results

Figure 5. Double-pulsed particle images, velocity profile, and distributed shear stress (from top to bottom) of the flow chamber without endothelial cells seeded

A flow chamber is designed so that a few glass slides with endothelial cells seeded on the top surface can be placed on the bottom of fluid channel. The fluid flow through the micro channel can be recorded by PIV which will render an actual image of the flow profile as well as the estimated shear stress.

Figure 3. Four basic tissues in the wall of aorta and true capillary (Physiol. Rev. 34:619-642, 1944)

X/L

Y/L

2 2.5 3 3.5 40

0.5

1

1.5

Shearstress: 0 2.30769 4.61538 6.92308 9.23077

Figure 6. Shear stress on glass slide without endothelial cells seeded at Y=0 and glass slide with endothelial cells seeded at Y=1.

Vascular DiseaseVascular Disease Vascular DiseaseVascular Disease

Endothelial CellEndothelial CellInjury / DysfunctionInjury / Dysfunction

Endothelial CellEndothelial CellInjury / DysfunctionInjury / Dysfunction

Altered Blood FlowAltered Blood Flow Altered Blood FlowAltered Blood Flow

Figure 2. Schematic diagram of the hypothesis

The altered or sickened endothelial cells can cause a tremendous change in blood flow within the scale of capillaries and it is reasonable to anticipate such results.

Reduced shear stress on the endothelial cell covered side (Y=1) versus the uncovered wall (Y=0) was observed. This preliminary data shows that an endothelial cell monolayer may cause a reduction in wall shear stress.

Conclusion and Future Plans

Motion of cations generate Motion of cations generate charge on the surfacecharge on the surface

Motion of cations generate Motion of cations generate charge on the surfacecharge on the surface

Mechanical strains cause motion Mechanical strains cause motion among cations in among cations in

the polymer membranethe polymer membrane

Mechanical strains cause motion Mechanical strains cause motion among cations in among cations in

the polymer membranethe polymer membrane

DuPontDuPontTMTM Nafion Nafion®® Polymer Polymer[Poly (perfluorosulfonic acid) ion [Poly (perfluorosulfonic acid) ion

exchange membrane]exchange membrane]

DuPontDuPontTMTM Nafion Nafion®® Polymer Polymer[Poly (perfluorosulfonic acid) ion [Poly (perfluorosulfonic acid) ion

exchange membrane]exchange membrane]

Charge is detected as a voltage signal Charge is detected as a voltage signal

Subsequently this effort will be followed with 3D blood vessel scaffold and application of the Active Polymer Ionic Shear Stress Sensor.