Bioengineering Seminar Schedule
Fall, 2005 (For prior semesters, click here: Fall
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Thursday, July 28, 2005, 10:00 - 11:00 am, Room 210 Hallowell Building, CG623 Hershey
Aashiish Agnihotri
Final Defense
"Molecular Level Interactions Between Blood-Components and Model Biomaterials Studied by
Atomic Force Microscopy"
Abstract
Fibrinogen is a key plasma protein involved in initiation of thrombosis on synthetic surfaces, and its adsorption
to the biomaterial surface and subsequent interactions with the blood platelets are of fundamental interest in
biomaterials development. In this work the influence of surface properties on the adsorption and activity of fibrinogen
has been investigated at the single molecule scale using atomic force microscopy (AFM). Tapping mode AFM was used
to study the time-dependent changes in the structure of fibrinogen under aqueous conditions following adsorption
on two model surfaces:
hydrophobic graphite and hydrophilic mica. Spreading kinetics of fibrinogen on the two surfaces was determined
by measuring the heights of the D and E domains of individual molecules over a time-period of ~2 hours. With the
objective of relating the observed post-adsorption structural changes to the surface availability of active epitopes
and extending AFM imaging studies to complex multicomponent protein films, the adhesion mapping mode of AFM was
developed for biologically sensitive imaging. The successful application was demonstrated by performing fibrinogen
recognition imaging in patterned dual-component protein films and randomly distributed dual-component protein films.
The effect of surface properties on the activity of fibrinogen was studied by measuring the interactions between
the platelet membrane integrin GPIIbIIIa and fibrinogen adsorbed to model hydrophilic and hydrophobic surfaces
by using the force mode of AFM. Taken together, this work adds to the current knowledge of surface thrombogenesis
by improving understanding of the molecular events that occur during blood-material interactions.
Friday, September 2, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Andrew Hoskins
Mechanical & Nuclear Engineering Biomechanics Lab, Penn State University
"Robotic Simulations of the Stance Phase of Human Walking in Cadaveric Lower Extremities"
Abstract
Investigating cadaver specimens has been instrumental in achieving our current understanding of bon and joint
mechanics in health and disease. As technology advances, cadaver experiments increase in complexity. The focus
of this talk will be the development of the Robotic Dynamic Activity Simulator, a device designed to create the
physiological loading environments of dynamic activities within cadaver specimens so that researchers can conduct
invasive investigations into foot and ankle function without endangering living subjects. The discussion will cover
the physiologic processes that have been included in the model and how they are manifested within the device. The
fidelity of the simulated environment produced with this device determines the transferability of experimental
findings to living tissue and common measures of the simulator's performance will be presented.
Friday, September 9, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Xiaofeng Zhang
Post Doctoral Fellow, Bioengineering
"Simultaneous Integrated Diffuse Optical Tomography and Functional Magnetic Resonance Imaging
of the Human Brain"
Abstract
A complete methodology has been developed to integrate simultaneous diffuse optical tomography (DOT) and functional magnetic resonance imaging (fMRI) measurements. This includes development of an MRI-compatible optical probe and a method for accurate estimation of the positions of the source and detector optodes in the presence of subjectspecific geometric deformations of the optical probe. Subject-specific head models are generated by segmentation of structural MR images. DOT image reconstruction involves solution of the forward problem of light transport in the head using Monte Carlo simulations, and inversion of the linearized problem for small perturbations of the absorption coefficient. Initial results show good co-localization between the DOT images of changes in oxy- and deoxyhemoglobin concentration and functional MRI data. The experimental data indicates that besides the changes in deoxyhemoglobin concentration, the changes in oxyhemoglobin concentration is also playing a secondary role in the blood oxygenation level dependent (BOLD) fMRI signal.
Friday, September 16, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Kendra Sharp
Assistant Professor of Mechanical & Nuclear Engineering
"Particle Behavior in Pressure-Driven and Electrokinetic Microfluidic Systems"
Friday, September 23, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Ki H. Chon
SUNY @ Stonybrook
"Development of a Cardiovascular Monitor and Sensor: from Hardware to Software"
Abstract
The cardiac autonomic nervous system is responsible for maintaining proper homeostasis, or balance, of the cardiovascular
system. One of our major areas of research is to detect, quantify, and interpret differences in dynamic characteristics
of the cardiac autonomic nervous system between normal and diseased subjects, in an attempt to find a marker for
increased risk of sudden cardiac death. Identifying and quantifying differences in the dynamic characteristics
of autonomic function between normal and diseased conditions may lead to a better understanding of the role of
autonomic function imbalance in diseased conditions, and should have important clinical diagnostic and prognostic
applications. Another active research area is the development of computational modeling approaches to understand
differences in dynamics of renal autoregulatory mechanisms between normotensive and hypertensive conditions. Both
hardware implementations and novel software data analysis techniques which we are using to achieve these research
objectives will be presented. For the hardware development, a personal digital assistant device to obtain on-line
and real-time data acquisition of ECG signals will be demonstrated. For software development, novel linear and
nonlinear time-varying signal processing techniques that can be successfully applied to cardiovascular and renal
data to differentiate between normal and diseased conditions will be demonstrated.
Friday, September 30, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
No Seminar BMES Conference
Friday, October 7, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Yangrong Zhang
Final Defense
"The Two Motor Domains of Kinesin-2 Coordinate for Processive Motility"
Abstract
The long-term goal of this project is to understand the fundamental mechanism of chemical and mechanical coordination between the two motor subunits of cytoskeletal motor proteins by studying Kinesin-2, one class of kinesins involved in the anterograde intraflagellar transport and unique among the kinesin superfamily in having two different motor domains. Despite a body of both in vivo and in vitro work on Kinesin-2 structure and function, it is still not clear why Kinesin-2 motors have two different heads. Our hypothesis is that the two heads are biochemically tuned to maximize motor function such as speed, strength, processivity and microtubule affinity. To test this hypothesis, we focused on KIF3A/B, the mouse ortholog of Kinesin-2, and constructed two homodimeric KIF3 motors by fusing the head of one chain to the rod-tail of the other. In microtubule gliding assays the two homodimeric motors moved at 10-fold different rates. Regarding the stepping rate of the wild-type KIF3A/B, the data are consistent with a coordinated head model in which detachment of the slow KIF3A head from the microtubule is accelerated roughly three-fold by the KIF3B head. However later on, we found that the huge motility difference of the two heads was possibly due to point mutations embedded in the A head. For studies with higher resolution techniques, we made fluorescence labeled heterodimeric and homodimeric KIF3 motors by replacing the tail domains with EGFP fusion proteins. The run length (processivity), dwell time, velocity of motors running on microtubules were characterized by total internal reflection fluorescence microscopy (TIRF) at single molecule level. The results showed that the A head was slightly more processive than the B head, with both less processive than conventional kinesins. The dynamic and kinetic interaction of motor-microtubule was investigated in a fast time scale by monitoring the rapid rotational diffusion in time-resolved fluorescence anisotropy and in a slow time scale by measuring the translational diffusion in fluorescence correlation spectroscopy (FCS). We successfully applied FCS in determining equilibrium dissociation rate constant of kinesin binding to microtubule by quantitating fractions of the fast diffused component (motor) and slowly diffused component (motor-microtubule complex). The measured processivity and stepping rates were incorporated into kinetic schemes for the kinesin chemomechanical cycle and were correlated with Monte Carlo simulation results, supporting a model called ATP Induced Detachment (AID) in which the intramolecular strain and conformation change induced by the binding of ATP to the front bound head is required for detaching the rear head from the microtubule.
Friday, October 14, 12 Noon - 1:00 pm, Room 210 Hallowell, CG624E Hershey
Osama Al-Bataineh
Final Defense
"A Transrectal Ultrasound Phased Array Applicator for Hyperthermia Treatment of Prostate Cancer"
Abstract
Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43 C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This imposes specific ultrasound transducer design requirements. Although phased arrays have been previously used to overcome the inability of nearfield focusing of large cylindrical piezoelectric transducers, the lack of an acoustically inhomogeneous three dimensional (3D) prostate model and economical computational methods have made it difficult to predict the appropriate shape of the array for better focusing and steering. This research utilizes the k-space computational method and a 3D, inhomogeneous, large scale, and coarse grid human prostate model to design an intracavitary probe for hyperthermia treatment of prostate cancer. Magnetic resonance imaging (MRI) thermometry and automatic feedback controlling were also used to accomplish the therapy. To achieve this, a 3D prostate model utilizing imaging data from the Visible Human Project was used to determine acoustical parameters of glandular, connective, fat, and muscle tissues. The acoustical model, included sound speed, density, and absorption parameters, was determined depending on optical parameters of each pixel of image layers. The k-space computational method used this coarse grid and inhomogeneous tissue model to simulate ultrasound wave propagation to predict the steady state pressure wavefield of the designed phased array. To insure the uniformity and spread of the pressure in the length of the array, and the steering and focusing capability in the width of the array, the equal sized elements of the phased array were 1 mm x 14 mm. The anatomical measurements of the prostate were used to predict the final phased array specifications (4 x 20 planar array, 1.2 MHz, element size = 1 mm x 14 mm, array size = 56 mm x 20 mm). A single input single output, switching, feedback controller was developed to control hyperthermia temperatures from the probe. Good agreement between the exposimetry and the k-space computational method results was shown. As an example, the -3 dB distances of the focal volume were 22.0 and 20.0 mm in the propagation direction for k-space prostate simulation and exposimetry results, respectively. Temperature simulations indicated that the rectal wall temperature was elevated less than 2 C during hyperthermia treatment. Steering and focusing ability of the designed probe in both azimuth and propagation directions were found to span the whole prostate volume with minimal grating lobes ( 10 dB reduction from the main lobe) and least heat damage to the rectal wall. Ex-vivo controlled hyperthermia experiments showed that the rise time was reduced by a factor of two when doubling the driving power. With a desired temperature plateau of 43.0 C, the MRI temperature results at the steady state were 42.9 0.38 C and 43.1 0.80 C for ex-vivo and in-vivo experiments, respectively. Unlike conventional computational methods, the k-space method provides powerful tool to predict pressure wavefield and temperature rise in sophisticated, large scale, 3D, inhomogeneous and coarse grid models. [Research supported by the Department of Defense Congressionally Directed Medical Prostate Cancer Research Program.]
Friday, October 21, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Edgar Meyhofer
University of Michigan
"Biomolecular Motors: From Single Molecules to Molecular Bio-Nanotechnology"
Abstract
Biomolecular motors are cellular protein machines that use the free energy derived from the hydrolysis of ATP
and interact with cytoskeletal filaments to generate motility. Myosin (from muscle cells) and kinesin (an organelle
transporter in cells) are the best known cellular motor molecules. Our long term interest in these motors is to
understand in detail the molecular principles underlying force and displacements generation as well as the molecular
mechanisms that control or modulate the activity, processivity, directionality and speed of biomotors in cells.
Our fundamental strategy to study these mechanisms is to combine protein engineering and a variety of single molecule
in vitro and in vivo measurements to directly observe individual molecules and quantify their mechanical and biophysical
properties. I will present work on the role of the myosin's neck domain in the generation of step displacements
and the molecular mechanism of processivity and speed in kinesins.
A second major research effort in the lab aims to use biomolecular motors in engineering applications: it is our
goal to seamlessly integrate biomolecular motors, cytoskeletal proteins, specific protein binding domains and antibodies
into microengineered systems to create extremely low power, biologically-based molecular sorters and detectors,
microscopic engines and transporters, and micro- and nano-fluidics pumps. As a first step towards such nanotechnological
applications, we have designed and implemented a first generation kinesin and microtubule-based pump and several
molecular sorters. These devices operate at power consumptions between 10 - 100 fW, sort more than 5000 molecules/s
and detect (sub)nano- to micromolar concentrations of analyte molecules. We are now working towards a vision of
"intelligent" biomolecular sorters and actuators that support cargo-specific functionality.
Friday,October 28, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Xiaomei Liu
Final Defense
"Environmental Influence on Osteoblastic Cell Growth in Vitro: From Phenotype to Genotype"
Abstract
Extended human life span and higher activity levels at later age have greatly increased need for orthopedic
healthcare. Improved hard-tissue repair, augmentation, or replacement has thus become a significant challenge for
orthopedic biomaterials and orthopedic surgery, as well as a need that is driving orthopedic tissue engineering.
The design/development of new generation of orthopedic biomaterials largely depends on establishing relationships
(so-called structure-property relationships) between material characteristics and the nature of the interactions
with hard-tissue cells (osteoblasts, osteoclasts, chondrocytes, etc.). However, the complex cellular and molecular
events that occur on the cell-material interface are still poorly understood. Thus the research hypothesis is that
cell/protein-mediated remodeling of bone can be quantified in vitro using a combination of genomic, proteomic,
and cellomic tools of investigation. A model osteoblastic cell line hFOB 1.19 (conditionally immortalized human
fetal osteoblast) was examined for short- and medium-term interactions with materials of varying surface chemistry/energy.
Results revealed a strong correlation of cell attachment and proliferation (cytocompatibility) with substratum
surface energy in a manner paralleling that previously observed with soft-tissue cells. Interestingly, hFOB attachment
and proliferation to fully-water-wettable glass were reproducibly less than that to tissue-culture-grade polystyrene
(TCPS) whereas attachment to fully-water-wettable quartz was significantly higher than TCPS. Morphological analysis
through SEM and immunofluorescent images indicates that hFOB discrimination against hydrophobic surfaces at early
stages of cell-substratum contact was substantially mitigated over time. Further analysis of integrin/protein expression
suggests that gene regulation leading to clear preference of hFOB for hydrophilic surfaces over hydrophobic counterparts
is particularly incisive at early stages (< 3 d) of cell-surface interactions but can persist for longer periods
for cells attached on very poorly cytocompatible surfaces. This research incorporating with physiochemical and
cellular/molecular approaches systematically investigated cell-material interactions in order to assemble structure-property
relationships. To further explore long-term microenvironmental influences on cell growth and development, two model
osteoblastic cell lines, hFOB 1.19 and MC3T3-E1 cells were cultured in an advanced bioreactor and conventional
tissue cultureware (TCPS). The results suggest that this bioreactor technique can sustain osteoblast culture up
to a period of 30 days with superior performance relative to TCPS. Therefore, this in vitro culture technique that
permits unattended long-term (weeks to months) culture within a stabilized and oxygenated culture environment shows
promise to be an idea tool for the study of long-term cell/protein-mediated bone remodeling, as well as cell-material/scaffold
interactions.
Friday, November 4, 12 :00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Student Presentations:
Chilman Bae
"Finite-Element Modeling of Cleft Resistance and Transmembrane Potential for Automated
Single-Cell Electroporation"
Abtract
Single cell electroporation (SCE) is a technique for insertion of dyes or other compounds into micron-scale regions of living cells through electric field-induced nano-sized membrane pores. We have developed an automated patch-clamp-based SCE system consisting of a computer-controlled motorized micromanipulator with a dye-filled micropipette. In our system, automation depends on real-time measurements of changes in cleft resistance (Rcl, the resistance between the tip of the pipette and the cell membrane) with feedback control of the pipette position. The quantitative relationships of cleft size and resistance, transmembrane potential and cleft size, and transmembrane potential and axial distance were determined using finite element analysis of current density and electric potential in the cleft using measured pipette geometries and a realistic endothelial cell properties. Increases in resistance with decreasing cleft size suggest that resistance measurements can be used to detect cleft size and to control pipette movement. When cleft size was in the order of 100nm, pore-inducing transmembrane potential (>0.2V) upon pipette pulse voltages of -8V was achieved. In addition, this simulation suggests that pores are locally formed on the membrane area of inner pipette lumen. Thus, finite element modeling shows that cleft resistance and transmembrane potential measurements provide the means to determine the pulse amplitudes necessary for membrane pore formation and to measure pipette proximity to adherent cells thus overcoming limitations of optical microscopy.
===========================================================================================
Meghan Hoskins
"Human Neutrophil Interactions with Cancer Cells"
Abstract
Previous experimental work has shown that melanoma cells are more likely to migrate through the endothelium
in a flow field in the presence of human neutrophils, or PMNs. Melanoma cells do not express molecules necessary
to adhere to the endothelium, however they do express ICAM-1, which is a molecule that adheres to the b2-integrins expressed by PMNs. The fact that PMNs do adhere to the endothelium led to the postulation
that tumor cells gain access to the endothelium and migrate out of the bloodstream by binding to PMNs that have
already adhered to the endothelium. To study the interactions between a melanoma cell and an adhered PMN, a computational
fluid dynamics model is being developed. In order to model the interactions between PMNs and melanoma cells, the
binding properties of the involved molecules need to be estimated. Thus, parallel plate flow chamber experiments
were performed and the binding and unbinding rates of PMNs to melanoma cells, quantified as kon0 and koff0, were calculated.
===========================================================================================
Luke Herbertson
"Flow Structures Generated by Mechanical Heart Valve Closure"
Abstract
The closing dynamics of a Bjork-Shiley Monostrut mechanical heart valve have been investigated using two-component laser Doppler velocimetry. Modifications to the valve housing have allowed for data acquisition very close to the point of impact. The studies were performed for the valve in the mitral position within an acrylic single-shot chamber. The system was driven by a pneumatic pump. Results indicate that the velocities, shear rates, Reynolds stresses and turbulence intensities observed are capable of inducing hemolysis. Vortices captured on the atrial side of the valve may contribute to cavitation, a phenomenon linked to stable bubbles (microembolic signals) and stroke in patients during and after mechanical heart valve implantation.
Friday, November 11, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Michael Sacks
University of Pittsburgh
"Biomechanics of Native and Engineered Heart Valve Tissues"
Abstract
On the most basic functional level, the aortic heart valve is essentially a check-valve that serves to prevent
retrograde blood flow from the aorta back into the left ventricle. This seemingly simple function belies the structural
complexity, elegant solid-fluid mechanical interaction, and durability necessary for normal aortic valve function.
For example, the aortic valve is capable of withstanding 30-40 million cycles per year, resulting in a total of
~3 billion cycles in single lifetime. No valve made from non-living materials has been able to demonstrate comparable
functional performance and durability. However, this staggering level of performance can be cut short by aortic
valve disease, the most common form being stenosis resulting from calcification. Currently, the treatment of aortic
valve disease is usually complete valve replacement. First performed successfully in 1960, surgical replacement
of diseased human heart valves by valve prostheses is now commonplace and enhances survival and quality of life
for many patients. However, they continue to have significant clinical problems and there is a profound need for
new approaches to valve therapies based on sound scientific and engineering principals. The focus of this talk
is to present our work on the biomechanical behavior of native and engineered heart valve tissues. In particular,
for engineered heart valve tissues many challenges exist to understand the intricate microstructure and the concomitant
complexity of mechanical interactions occurring between scaffold, cellular, and extracellular matrix constituents.
Mathematical models that simulate the composite mechanical behavior of the scaffold and the developing tissue could
potentially facilitate the design of engineered tissues and mechanical conditioning regimens. Such models could
thus play a pivotal role in the design and development of an engineered heart valve.
Friday, November 18, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Michael McShane
Louisiana Technology University
"Microcapsule Biochemical Sensors: Assembling Molecules into Useful Micro/Nanosystems"
Abstract
Metabolic monitoring has become a primary goal for understanding basic physiological processes as well as managing
diseases, detecting microorganisms, etc. "Smart tattoos"- optically-active microparticles designed for
implantation in skin interstitium are attractive systems with potential to enable frequent analysis of tissue chemistry
via noninvasive transdermal interrogation. A key issue in the design and construction of such biosensors is the
integration of catalytic agents, sensing components, and matrix materials into an architecture that controls transport
rates through a process that is simple and reliable. Multiple approaches to creating these systems are being pursued,
each of which uses self-assembly methods to form polymer microcapsules containing fluorescent assay chemistry.
This presentation will cover the development and current status of two novel systems for biochemical analysis,
using enzymatic and competitive-binding (non-consuming) approaches, using glucose as a model target analyte. The
design, fabrication, and characterization of the two systems will be discussed from theoretical and practical views.
First, the requirements for micro/nanoscale enzymatic optical biosensors employing oxygen indicators will be discussed
from the viewpoint of balancing the microscale diffusion and reaction of the co-substrates, and characterization
of sensor prototypes and model validation will be discussed. Second, the fabrication and analytical performance
evaluation of a new near-infrared competitive-binding assay packaged within microcapsules will be presented. Both
systems have been successfully demonstrated to respond sensitively and reversibly to glucose under static and dynamic
in vitro conditions. Finally, the roadmap to in vivo deployment and extension of the glucose biosensor concepts
for monitoring other analytes will be discussed.
Friday, November 25, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
No Seminar - Thanksgiving Break
Friday, December 2, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Jennie Leach
University of Maryland
"Tissue-Mimetic Materials Engineering: Strategies to Capture the Functional Properties of
Native Tissues"
Abstract
Natural macromolecules are an enormously diverse and complex class of materials. These proteins and carbohydrates have evolved to perform very specific biochemical, mechanical and structural roles. Though great strides have been made towards capturing these properties in synthetic polymers, we are still far from creating synthetics that possess the advantages inherently presented by natural biomaterials. Hierarchical structures, for example, are ubiquitous in nature where biomolecules are often self-assembled into composite materials designed for multifunctional applications. Notably, collagen is self-assembled from the nano- to micro- to macro-scale, resulting in extraordinarily high-strength fibers in tendon. We aim to develop enabling tools for engineering naturally-derived biomolecules into materials that mimic the structure and function of native tissues. Results from three main areas of biomaterials development will be presented: 1) photopolymerizable hyaluronic acid-based materials for soft tissue engineering, 2) nano-aligned collagen matrices using microfluidics, and 3) tissue-mimetic hydrogels for investigating force-dependent breast cancer growth and malignancy. Methods to fine-tune material biochemical, mechanical and structural properties and their impact on cell behavior will be discussed.
Friday, December 9, 12:00 - 1:10 pm, Room 210 Hallowell, CG624E Hershey
Maruti Uppalapati
"Controlling and Confining Kinesin Driven Microtubules in Capped Microchannels"
Abstract
In eukaryotic cells, kinesin motor proteins transport cargo and provide the mechanical forces underlying mitotic
meiotic spindle morphogenesis and chromosome separation. A continuing challenge in nanoscience is controlling the
manipulation and assembly of materials at the nano-scale, and the kinesin-microtubule system provides a model system
for force generation and nano-scale motion. Here we demonstrate a novel method for microtubule confinement and
for generating a high density ensemble of isopolar microtubules. This approach can be used to concentrate aligned
microtubules for microscale transport applications.
=============================================================================================================================
Jeff Garanich
Final Defense
"The Role of Vascular Smooth Muscle Cells and Adventitial Fibroblasts in Flow-Mediated
Mechanisms of Intimal Hyperplasia and Arterialization"
Abstract
Smooth muscle cell (SMC) proliferation and migration are hallmarks of intimal hyperplasia (IH) following vascular
injury. Previous work has shown that intimal lesion progression is affected by local hemodynamics. These observations,
coupled with the fact that SMCs are exposed to blood flow in both denuded vessels (direct contact with flowing
blood) and intact vessels (interstitial blood flow driven by the transmural pressure gradient), motivate this study
of the role of fluid flow shear stress (SS) on SMC migration. While several in vitro studies have evaluated the
effect of SS on SMC proliferation, the influence of SS on SMC migration has yet to be determined. Rat aortic SMCs
were therefore seeded on porous Matrigel-coated cell culture inserts and exposed to 1, 10, or 20 dyn/cm2
SS for 1-4 h with a rotating disk apparatus. Four h of either 10 or 20 dyn/cm2 SS significantly inhibited
SMC migration through the Matrigel layer to the underside of the insert and this inhibition was associated with
the nitric oxide-mediated downregulation of SMC matrix metalloproteinase (MMP)-2 activity. Western blots showed
no effect of 4 h of 20 dyn/cm2 SS on SMC production of platelet-derived growth factor-AA, another chemical
known to suppress SMC migration.
The ability of vascular fibroblasts (FBs) to modulate their phenotype to smooth muscle (SM)-like myofibroblasts
(myoFBs) and the involvement of these cell populations in physiologic and pathologic processes on both the macrocirculatory
(IH) and microcirculatory (capillary arterialization) levels motivate the current study into the effects of mechanical
and chemical stimulation on FB and myoFB function. Because FBs are subjected to interstitial flow (SS) in both
large and small vessels, it is important to evaluate the effect of SS on FB and myoFB migration, which participate
in IH and arterialization. In studies similar to those described above for SMCs, 4 h of 20 dyn/cm2 SS
significantly enhanced rat aortic FB migration while it suppressed myoFB migratory activity. The contractile responses
of serum-starved FBs and myoFBs to an interstitial fluid solute (serum) were also determined. Re-exposure to 2%
serum elicited significant contraction of myoFBs within 2 minutes of stimulation while it had no significant effect
on FB contractility up to one hour following exposure. These data suggest that modulation of FB phenotype appears
to be one way to regulate their involvement in both physiologic and pathologic processes.
For additional information, contact Ms. Doretta Garvey, Dept
of Bioengineering, Tel: 814.865.1407 or E-Mail: bioe@engr.Professor, Biomedical Engineering
psu.edu