39 research outputs found
The role of hydrodynamic interactions in the dynamics and viscoelasticity of actin networks
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 143-146).Actin, the primary component of the cytoskeleton, is the most studied semi-flexible filament, yet its dynamics remains elusive. We show that hydrodynamic interactions (HIs) significantly alter the time scale of actin deformation by 2-20 fold at different levels of network structure. For a single fiber, HIs between the mesh-sized segments can change the net force by up to 7 fold. Relaxation times are underestimated, if HIs are ignored, but mode shapes are not affected. HIs can explain deviation of the relaxation times from standard worm like chain models, speculated to be due to internal viscosity of the filament. HIs affect filament alignment, a necessary step for bundle formation. Ignoring HIs can result in up to 20-fold overestimation of shear loss modulus in the 2 ym range investigated. Even for a 1 mg/ml F-actin (0.1% volume fraction), HIs cannot be neglected whether the network is discretized into beads or rods. A shear loss modulus, slightly dependent on system-size, can be defined consistent with (intrinsic) viscoelasticity. However, axial loss modulus follows a quadratic system-size dependency consistent with poroelasticity. Our results suggest that including HIs is critical for consistency in theoretical models or analyzing experimental observation in cytoskeleton mechanics and dynamics. We also propose a new rod method to incorporate the HIs accurately and effectively. This method includes HIs in the larger systems, the same way as typical bead models, but it can decrease the computational cost by up to 100,000 fold. The primary part of this thesis deals with the viscous properties of the cytoskeletal actin networks investigated via theoretical bottom-up approaches in the nm to pm ranges. However, initially we focus on elastic properties of arterial tissue in the pm to mm ranges via an experimental top-down approach. We develop a combined robust registration and inverse elasticity method to investigate the mechanical properties of arterial tissue. We quantify the accuracy of this method with simulated problems and in vitro gels. This method can identify lipid pools via OCT (optical coherence tomography) and assess plaque rupture risk for cardiovascular diagnosis. The method can also be used as a model-based registration technique.Key words: Actin, Hydrodynamic Interactions, Relaxation Time, Cytoskeleton, Rod Model, Brownian Dynamics, Viscoelasticity, Poroelasticity, Length-Scale Dependent, Inverse Elasticity Problem, Registration, Optical Coherence Tomography (OCT), Atherosclerotic Plaque, Cardiovascular Mechanics.by Reza Karimi.Ph.D
Frequency composition of wall shear stress in animal models of atherosclerosis
Atherosclerosis and plaque rupture are widely known as multifactorial problems. To
isolate the significance of wall shear stress in these problems, the work of this thesis
explores the hypothesis that the frequency composition of the wall shear stress signal
is associated with the different plaque compositions and disease characteristics in
animal models of atherosclerosis.
In this thesis, a lattice Boltzmann simulation tool was developed to test the hypothesis
with the basic functionality of an existing code being enhanced for blood flow
simulation and wall shear stress calculation. The wall shear stress signals computed
from the simulation tool were analysed in terms of the frequency composition to
recover the harmonic amplitude and phase information. This information was then
used in comparing the different animal models.
Compared to the healthy, non-diseased vessel, disease models are known to result in a
decrease in the time-averaged wall shear stress from the reduction in blood flow rate
and local complex flow patterns. Further to this, the simulation of these models showed
a decrease in the first harmonic amplitude along the length of the vessel. This is a key
result of this thesis as the decreased first harmonic amplitude is associated with an
increase in the expression of adhesion molecules and proinflammatory factors in
endothelial cells. The uniformity in wall shear stress in regions of different plaque
type, however, suggests the dominance of circumferential stretch effects over wall
shear stress effects in the disease process.
Blood flow simulations in the mouse, rabbit and human vessels were also performed
to deduce scaling relationships of the zeroth and first harmonic amplitudes between
mammals. The body mass exponent of the first harmonic amplitude was found to be
higher than that of the zeroth harmonic amplitude. This suggests an increased
significance of the first harmonic component in the wall shear stress signal relative to
the zeroth harmonic amplitude in larger mammals. The absence of plaque rupture in
the atherosclerotic minipig, however, also suggests the dominance of genomic effects
over wall shear stress effects in the disease process.
A key issue in atherosclerosis research is the absence of plaque rupture in the mouse
model. The apparent dominance of circumferential stretch and genomic differences
shown here suggests that the wall shear stress alone cannot explain the lack of plaque
rupture in atherosclerotic mice. How these differences affect plaque composition
would be key in understanding the absence of plaque rupture in mouse models and
how studies in mice can be applied to benefit human treatments
Analysis of Blood Flow in Patient-specific Models of Type B Aortic Dissection
Aortic dissection is the most common acute catastrophic event affecting the aorta. The
majority of patients presenting with an uncomplicated type B dissection are treated
medically, but 25% of these patients develop subsequent dilatation and aortic aneurysm
formation. The reasons behind the longâterm outcomes of type B aortic dissection are
poorly understood. As haemodynamic factors have been involved in the development
and progression of a variety of cardiovascular diseases, the flow phenomena and
environment in patientâspecific models of type B aortic dissection have been studied in
this thesis by applying computational fluid dynamics (CFD) to in vivo data. The present
study aims to gain more detailed knowledge of the links between morphology, flow
characteristics and clinical outcomes in type B dissection patients.
The thesis includes two parts of patientâspecific study: a multiple case crossâsectional
study and a single case longitudinal study. The multiple cases study involved a group of
ten patients with classic type B aortic dissection with a focus on examining the flow
characteristics as well as the role of morphological factors in determining the flow
patterns and haemodynamic parameters. The single case study was based on a series of
followâup scans of a patient who has a stable dissection, with an aim to identify the
specified haemodynamic factors that are associated with the progression of aortic
dissection. Both studies were carried out based on computed tomography images
acquired from the patients. 4D Phaseâcontrast magnetic resonance imaging was
performed on a typical type B aortic dissection patient to provide detailed flow data for
validation purpose. This was achieved by qualitative and quantitative comparisons of
velocityâencoded images with simulation results of the CFD model.
The analysis of simulation results, including velocity, wall shear stress and turbulence
intensity profiles, demonstrates certain correlations between the morphological
features and haemodynamic factors, and also their effects on longâterm outcomes of
type B aortic dissections. The simulation results were in good agreement with in vivo
MR flow data in the patientâspecific validation case, giving credence to the application of
the computational model to the study of flow conditions in aortic dissection. This study
made an important contribution by identifying the role of certain morphological and
haemodynamic factors in the development of type B aortic dissection, which may help
provide a better guideline to assist surgeons in choosing optimal treatment protocol for
individual patient
Subharmonic Venture
As a person, always fascinated with the presence of physics in the daily life
challenges, let me share this
Molecular Imaging
The present book gives an exceptional overview of molecular imaging. Practical approach represents the red thread through the whole book, covering at the same time detailed background information that goes very deep into molecular as well as cellular level. Ideas how molecular imaging will develop in the near future present a special delicacy. This should be of special interest as the contributors are members of leading research groups from all over the world
Oscillatory wall strain reduction precedes arterial intimal hyperplasia in a murine model
Cardiovascular diseases (CVD) remain the most common cause of death in the United States. Additionally, peripheral artery disease affects thousands of people each year. A major underlying cause of these diseases is the occlusion of the coronary or peripheral arteries due to arteriosclerosis. To overcome this, a number of vascular interventions have been developed including angioplasty, stenting, endarterectomies and bypass grafts. Although all of these methods are capable of restoring blood flow to the distal organ after occlusion, they are all plagued by unacceptably high restenosis rates. While the biological reactions that occur as a result of each of these methods differ, the initiating factor of both the primary atherosclerosis and subsequent failure of vascular interventions appears to be intimal hyperplasia (IH).
Intimal hyperplasia is most simply defined as the expansion of multiple layers of cells internally to the internal elastic lamina of the blood vessel. This excessive cellular growth leads to arterial stenosis, plaque formation and inflammatory reactions. Despite extensive research the underlying factors that cause IH remain unclear. A quantity of research to date has implicated endothelial cell mechanosensation as the mechanism by which IH is initiated with evidence positively correlating wall shear stress with IH. Others, however, have demonstrated that changes in the stresses applied to the wall in vitro can modulate IH independent of hemodynamic shear stress. Thus, relations between wall tensile stress and IH in vivo may shed light on the underlying mechanisms of IH. Since noninvasive measurement of wall tensile stress in vivo is difficult, it is most feasible to measure oscillatory wall strain which is intimately related to wall tensile stress through the mechanical properties of the arterial wall. In this dissertation, we hypothesize that reductions in oscillatory wall strain precede the formation of intimal hyperplasia in a murine model.
To test our hypothesis, we first developed a novel, high spatial and temporal resolution method to measure oscillatory wall strains in the murine common carotid artery. We validated this method both in vitro using an arterial phantom and in vivo using a murine model of abdominal aortic aneurysms. To assess relationships between strain and IH, we applied our strain measurement technique to a recently developed mouse model of IH. In this model, a suture is used to create a focal stenosis and reduce flow through the common carotid artery by 85%; resulting in proximal IH formation. Using this approach, we identified a relationship between oscillatory strain reductions and IH. Subsequent analysis demonstrated that early reductions in mechanical strain just 4 days after focal stenosis creation correlate with IH formation nearly 1 month later.
Since IH is not expected to form by day 4 in this model, we went on to assess changes in gross vascular morphology at day 4. We discovered that, although strains are significantly reduced by day 4, no significant IH can be observed, suggesting that changes in wall structure are resulting in strain reductions. At day 4 post-op, we observed cellular proliferation and leukocyte recruitment to the wall without intimal hyperplasia. These studies suggest that early reductions in mechanical strain may be an important predictor of IH formation. Clinically, this relation could be important for the development of novel techniques for predicting IH formation before it becomes hemodynamically significant
Washington University Senior Undergraduate Research Digest (WUURD), Spring 2018
From the Washington University Office of Undergraduate Research Digest (WUURD), Vol. 13, 05-01-2018. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Scien