© 2000 American Heart Association, Inc.
Vascular Biology |
Effect of Fluid Flow on Smooth Muscle Cells in a 3-Dimensional Collagen Gel Model
From the Biomolecular Transport Dynamics Laboratory, Departments of Chemical Engineering and Bioengineering, Pennsylvania State University, University Park, Pa.
Correspondence to Dr John M. Tarbell, The Pennsylvania State University, Departments of Chemical Engineering and Bioengineering, 155 Fenske Laboratory, University Park, PA 16802. E-mail jmt{at}psu.edu
Abstract—A 3D collagen gel model
was developed to simulate interstitial fluid flow and to
assess the importance of this flow on the biochemical
production rates of vascular smooth muscle cells (SMCs). Rat
aortic SMCs were suspended in type I collagen, and the gel was
supported by nylon fibers that allowed a 9-cm length of the SMC-gel
model to withstand 90 cm H2O differential pressure over a
6-hour period without significant compaction. Up to 1
dyne/cm2 shear stress on the suspended SMCs could be
induced by the pressure-driven interstitial flow. The
suspended SMCs were globular, had a diameter of 
10 µm, and
were distributed uniformly throughout the gel. The collagen fibers
formed a network that was connected randomly with the surface of SMCs
and nylon fibers. The diameter of the collagen fibers was 100 nm,
and the concentration of collagen was 2.5 mg/mL. Using these
parameters, fiber matrix theory predicted a Darcy
permeability coefficient (Kp) of
1.22x10-8 cm2, which was close to
the measured value of Kp. The
production rates of prostaglandin (PG)
I2 and PGE2 were used as markers of biochemical
responsiveness of SMCs to fluid shear stress. Both PGI2 and
PGE2 production rates under 1 dyne/cm2
shear stress were significantly elevated relative to static (no-flow)
controls. The production rates, however, were 10 times lower
than observed when the same cells were plated on collagen-treated glass
slides (2D model) and exposed to the same level of shear stress by use
of a rotating disk apparatus. The results indicate that
interstitial flow can affect SMC biology and that SMCs are
more quiescent in 3D cultures than in 2D cultures. The 3D collagen gel
model should be useful for future studies of interstitial
flow effects on SMC function.
Key Words: shear stress • smooth muscle cell • collagen gel • prostaglandin
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