Sharif Digital Repository

In this study, numerical simulation of collective cell migration is presented in order to mimic the group migration of endothelial cells subjected to the concentration gradients of a biochemical factor. The developed 2D model incorporates basic elements of the cell, including both the cell membrane and the cell cytoskeleton, based on a viscoelastic cell mechanic model. Various cell processes - including cell random walk, cell-cell interactions, cell chemotaxis, and cellular cytoskeleton rearrangements - are considered and analyzed in our developed model. After validating the model by using available experimental data, the model is used to investigate various important parameters during... 

Microfluidic devices have received wide attention and shown great potential in the field of tissue engineering and regenerative medicine. Investigating cell response to various stimulations is much more accurate and comprehensive with the aid of microfluidic devices. In this study, we introduced a microfluidic device by which the matrix density as a mechanical property and the concentration profile of a biochemical factor as a chemical property could be altered. Our microfluidic device has a cell tank and a cell culture chamber to mimic both 2D to 3D and 3D to 3D migration of three types of cells. Fluid shear stress is negligible on the cells and a stable concentration gradient can be... 

Flow mediated dilation (FMD) is a non-invasive method for endothelial function assessment providing an index extracted from ultrasonic B-mode images. Although utilized in the research community, the difficulty of its application and high cost of ultrasonic devices prevent it from being widely used in clinical settings. In this study we show that substituting the ultrasonic device with more easily handled and low cost photoplethysmography and electrocardiography is possible. We introduce new indices based on the photoplethysmogram (PPG) and electrocardiogram (ECG) and show that they are correlated with the ultrasound-based FMD Index. To this end, a conventional ultrasound FMD test was carried... 

Atherosclerosis is a world-spread and well-known disease. This disease strongly relates to the endothelial cells (ECs) function. Normally, the endothelial cells align in the flow direction in the atheroprotected sites; however, in the case of atheroprone sites these cells orient randomly. The mechanical stimuli such as wall shear stress and strains could determine the morphology and function of the endothelial cells. In the present study, we numerically simulated the left main coronary artery (LCA) and its branches to left anterior descending (LAD) and left circumflex coronary (LCX) artery using fluid-structure interaction (FSI) modeling. The results were presented as longitudinal and... 

In the recent years a great attention of research deals with different physical and biological aspects of the BBB structure, a robust shield that separates the blood and brain, a recent research held by the authors of this paper has focused on figuring out computing the diffusion coefficient of endothelial cell membrane. In this study, the major efforts have been concentrated on calculating a standardized measure for the amount of permeability and diffusion of this barrier. As a result, this work is dedicated to molecular dynamics (MD) simulation of calculating the interaction force between nano-particle and BBB membrane. data is recorded by using steered molecular dynamics simulation and... 

In an effort to identify a useful noninvasive screening tool for cardiovascular diseases (CVD) screening, photoplethysmograph (PPG) signals were acquired and analyzed. These PPG signals were recorded during reactive hyperemia experiments consisting of a 4-minute blood flow blockage of the right arm (RA) brachial artery (BA) using a blood pressure cuff inflator. This procedure is usually done for the assessment of endothelial dysfunction which is a risk factor for developing CVD. In this study, signals of the infrared (IR) and red (R) LED's of the PPG sensor were analyzed. These signals were preprocessed, normalized and slow varying component of the signal (DC values) and the pulsatile... 

The shape and morphology of endothelial cells (ECs) lining the blood vessels are a good indicator for atheroprone and atheroprotected sites. ECs of blood vessels experience both wall shear stress (WSS) and cyclic stretch (CS). These mechanical stimuli influence the shape and morphology of ECs. A few models have been proposed for predicting the morphology of ECs under WSS or CS. In the present study, a mathematical cell population model is developed to simulate the morphology of ECs under combined WSS and CS conditions. The model considers the cytoskeletal filaments, cell–cell interactions, and cell–extracellular matrix interactions. In addition, the reorientation and polymerization of... 

The function and morphology of Endothelial Cells (ECs) play a key role in atherosclerosis. The mechanical stimuli of ECs, such as Wall Shear Stress (WSS) and arterial wall strain, greatly inuence the function and morphology of these cells. The present article deals with computations of these stimuli for a 3D model of a healthy coronary artery bifurcation. The focus of the study is to propose an accurate method for computations of WSS and strains. Two approaches are considered: Coupled simultaneous simulation of arterial wall and blood flow, called fluid-Structure Interaction (FSI) simulation, and decoupled, which simulates each domain (fluid and solid domain) separately. The study... 

A cell migration numerical simulation is presented to mimic the motility of endothelial cells subjected to the concentration gradients of a Forebrain embryoniccortical neuron Conditioned Medium (CM). This factor was previously shflown to induce the directional chemotaxis of endothelial cells with an over-expressed G protein coupled receptor 124 (GPR 124). A cell simulator program incorporates basic elements of the cell cytoskeleton, including membrane, nucleus and cytoskeleton. The developed 2D cell model is capable of responding to concentration gradients of biochemical factors by changing the cytoskeleton arrangement. Random walk force, cell drag force and cell inertial effects are also... 

Various physical and biological aspects of the Blood Brain Barrier (BBB) structure still remain unfolded. Therefore, among the several mechanisms of drug delivery, only a few have succeeded in breaching this barrier, one of which is the use of Magnetic Nanoparticles (MNPs). However, a quantitative characterization of the BBB permeability is desirable to find an optimal magnetic force-field. In the present study, a molecular model of the BBB is introduced that precisely represents the interactions between MNPs and the membranes of Endothelial Cells (ECs) that form the BBB. Steered Molecular Dynamics (SMD) simulations of the BBB crossing phenomenon have been carried out. Mathematical modeling... 

Superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with antimicrobial agents are promising infection-targeted therapeutic platforms when coupled with external magnetic stimuli. These antimicrobial nanoparticles (NPs) may offer advantages in fighting intracellular pathogens as well as biomaterial-associated infections. This requires the development of NPs with high antimicrobial activity without interfering with the biology of mammalian cells. Here, we report the preparation of biocompatible antimicrobial SPION@gold core-shell NPs based on covalent immobilization of the antimicrobial peptide (AMP) cecropin melittin (CM) (the conjugate is named AMP-NP). The minimal inhibitory... 

A thorough understanding of determining factors in angiogenesis is a necessary step to control the development of new blood vessels. Extracellular matrix density is known to have a significant influence on cellular behaviors and consequently can regulate vessel formation. The utilization of experimental platforms in combination with numerical models can be a powerful method to explore the mechanisms of new capillary sprout formation. In this study, using an integrative method, the interplay between the matrix density and angiogenesis was investigated. Owing the fact that the extracellular matrix density is a global parameter that can affect other parameters such as pore size, stiffness,... 

Endothelial dysfunction, which can be noninvasively assessed by flow mediated vasodilation (FMD), predicts an increased rate of adverse cardiovascular events. The endothelial dysfunction is considered as a leading cause of development and progression of the atherosclerotic process. The main aim of this study is to review different non-invasive methods to assess the endothelial dysfunction and to propose enhancements to a new method based on photoplethysmography (PPG). First, non-invasive techniques developed for the evaluation of peripheral endothelial function (including the Doppler ultrasound (US)) will be reviewed. Although noninvasive, US -based techniques present a few disadvantages. To... 

Noninvasive measurement of brachial artery (BA) flow mediated dilation (FMD), commonly measured by high resolution ultrasonography, has provided a non-invasive means for the evaluation of endothelial function. Recently, another technique based on finger photopletysmogram (PPG) analysis has been proposed by the authors. In this paper, simultaneous measurement of BA FMD and PPG signals data from 86 human subjects (43 healthy and 43 risk) is analyzed and a statistical model is proposed to estimate the BA FMD based on PPG signals, the BA diameter at baseline as well as other demographics factors such as age and gender. Linear regression by multivariate analysis was conducted to obtain the... 

The morphology of endothelial cells (ECs) may be an indication for determining atheroprone sites. Until now, there has been no clinical imaging technique to visualize the morphology of ECs in the arteries. The present study introduces a computational technique for determining the morphology of ECs. This technique is a multiscale simulation consisting of the artery scale and the cell scale. The artery scale is a fluid-structure interaction simulation. The input for the artery scale is the geometry of the coronary artery, that is, the dynamic curvature of the artery due to the cardiac motion, blood flow, blood pressure, heart rate, and the mechanical properties of the blood and the arterial... 

Background: Understanding cancer development crossing several spatial-temporal scales is of great practical significance to better understand and treat cancers. It is difficult to tackle this challenge with pure biological means. Moreover, hybrid modeling techniques have been proposed that combine the advantages of the continuum and the discrete methods to model multiscale problems. Methods: In light of these problems, we have proposed a new hybrid vascular model to facilitate the multiscale modeling and simulation of cancer development with respect to the agent-based, cellular automata and machine learning methods. The purpose of this simulation is to create a dataset that can be used for... 

Nowadays, nanoparticles (NPs) are used in a variety of biomedical applications including brain disease diagnostics and subsequent treatments. Among the various types of NPs, magnetic nanoparticles (MNPs) have been implemented by many research groups for an array of life science applications. In this paper, we studied MNPs controlled delivery into the endothelial cells using a magnetic field. Dynamics equations of MNPs were defined in the continuous domain using control theory methods and were applied to crossing the cell membrane. This study, dedicated to clinical and biomedical research applications, offers a guideline for the generation of a magnetic field required for the delivery of... 

In this study, a new method for the simulation of the time-dependent behavior of actin cytoskeleton during cell shape change is proposed. For this purpose, a three-dimensional model of endothelial cell consisting of cell membrane, nucleus membrane, and main components of cytoskeleton, namely actin filaments, microtubules, and intermediate filaments is utilized. Actin binding proteins, which play a key role in regulating actin cytoskeleton behavior, are also simulated by using a novel technique. The actin cytoskeleton in this model is more dynamic and adoptable during cell deformation in comparison to previous models. The proposed model is subjected to compressive force between parallel micro... 

Nowadays, nanoparticles (NPs) are used in a variety of biomedical applications including brain disease diagnostics and subsequent treatments. Among the various types of NPs, magnetic nanoparticles (MNPs) have been implemented by many research groups for an array of life science applications. In this paper, we studied MNPs controlled delivery into the endothelial cells using a magnetic field. Dynamics equations of MNPs were defined in the continuous domain using control theory methods and were applied to crossing the cell membrane. This study, dedicated to clinical and biomedical research applications, offers a guideline for the generation of a magnetic field required for the delivery of... 

The main focus of this study is to address the possibility of using molecular dynamics (MD) simulation, as a computational framework, coupled with experimental assays, to optimize composite structures of a particular electrospun scaffold. To this aim, first, MD simulations were performed to obtain an initial theoretical insight into the capability of heterogeneous surfaces for protein adsorption. The surfaces were composed of six different blends of PVA (polyvinyl alcohol) and PCL (polycaprolactone) with completely unlike hydrophobicity. Next, MTT assay was performed on the electrospun scaffolds made from the same percentages of polymers as in MD models to gain an understanding of the...