scholarly journals Mechanical Interactions between a Cell and an Extracellular Environment Facilitate Durotactic Cell Migration

2018 ◽  
Author(s):  
Abdel-Rahman Hassan ◽  
Thomas Biel ◽  
Taeyoon Kim
Keyword(s):  
Cell Migration ◽  
Computational Models ◽  
Biomechanical Model ◽  
Coarse Grained ◽  
Physiological Processes ◽  
Specific Direction ◽  
A Cell ◽  
Stiffness Profile ◽  
Contractile Forces ◽  
Extracellular Environment

ABSTRACTCell migration is a fundamental process in biological systems, playing an important role for diverse physiological processes. Cells often exhibit directed migration in a specific direction in response to various types of cues. In particular, cells are able to sense the rigidity of surrounding environments and then migrate towards stiffer regions. To understand this mechanosensitive behavior called durotaxis, several computational models have been developed. However, most of the models made phenomenological assumptions to recapitulate durotactic behaviors, significantly limiting insights provided from these studies. In this study, we developed a computational biomechanical model without any phenomenological assumption to illuminate intrinsic mechanisms of durotactic behaviors of cells migrating on a two-dimensional substrate. The model consists of a simplified cell generating contractile forces and a deformable substrate coarse-grained into an irregular triangulated mesh. Using the model, we demonstrated that durotactic behaviors emerge from purely mechanical interactions between the cell and the underlying substrate. We investigated how durotactic migration is regulated by biophysical properties of the substrate, including elasticity, viscosity, and stiffness profile.

scholarly journals Random Walks of a Cell With Correlated Speed and Persistence Influenced by the Extracellular Topography

2021 ◽  
Vol 9 ◽  
Author(s):  
Kejie Chen ◽  
Kai-Rong Qin
Keyword(s):  
Cell Migration ◽  
Random Walk ◽  
Cell Types ◽  
Coarse Grained ◽  
Search Efficiency ◽  
Complex Environments ◽  
Unit Distance ◽  
Lévy Walk ◽  
Levy Walk ◽  
A Cell

Cell migration through extracellular matrices is critical to many physiological processes, such as tissue development, immunological response and cancer metastasis. Previous models including persistent random walk (PRW) and Lévy walk only explain the migratory dynamics of some cell types in a homogeneous environment. Recently, it was discovered that the intracellular actin flow can robustly ensure a universal coupling between cell migratory speed and persistence for a variety of cell types migrating in the in vitro assays and live tissues. However, effects of the correlation between speed and persistence on the macroscopic cell migration dynamics and patterns in complex environments are largely unknown. In this study, we developed a Monte Carlo random walk simulation to investigate the motility, the search ability and the search efficiency of a cell moving in both homogeneous and porous environments. The cell is simplified as a dimensionless particle, moving according to PRW, Lévy walk, random walk with linear speed-persistence correlation (linear RWSP) and random walk with nonlinear speed-persistence correlation (nonlinear RWSP). The coarse-grained analysis showed that the nonlinear RWSP achieved the largest motility in both homogeneous and porous environments. When a particle searches for targets, the nonlinear coupling of speed and persistence improves the search ability (i.e. find more targets in a fixed time period), but sacrifices the search efficiency (i.e. find less targets per unit distance). Moreover, both the convex and concave pores restrict particle motion, especially for the nonlinear RWSP and Lévy walk. Overall, our results demonstrate that the nonlinear correlation of speed and persistence has the potential to enhance the motility and searching properties in complex environments, and could serve as a starting point for more detailed studies of active particles in biological, engineering and social science fields.

scholarly journals Length of Mucin-Like Domains Enhance Cell-Ebola Virus Adhesion by Increasing Binding Probability

2020 ◽  
Author(s):  
X. Cui ◽  
N. Lapinski ◽  
X. Zhang ◽  
A. Jagota
Keyword(s):  
Ebola Virus ◽  
Molecular Model ◽  
Persistence Length ◽  
Experimental Studies ◽  
Coarse Grained ◽  
Physiological Processes ◽  
Initial Adhesion ◽  
Binding Probability ◽  
A Cell ◽  
Coated Surface

AbstractThe Ebola virus (EBOV) hijacks normal physiological processes by apoptotic mimicry in order to be taken up by the cell it infects. The initial adhesion of the virus to the cell is based on the interaction between T-cell immunoglobulin and mucin domain protein, TIM, on the cell-surface and phosphatidylserine (PS) on the viral outer surface. Therefore, it is important to understand the interaction between EBOV/PS and TIM, with selective blocking of the interaction as a potential therapy. Recent experimental studies have shown that for TIM-dependent EBOV entry, a Mucin-like Domain (MLD) with a length of at least 120 amino acids is required, possibly due to the increase of area of the PS-coated surface sampled. We examine this hypothesis by modeling the process of TIM-PS adhesion using a coarse-grained molecular model. We find that the strength of bound PS−TIM pairs is essentially independent of TIM length. TIMs with longer MLDs have higher average binding strengths because of an increase in the probability of binding between EBOV and TIM proteins. Similarly, we find that for larger persistence length (less flexible) the average binding force decreases, again because of a reduction in the probability of binding.Statement of SignificanceThis work studies the mechanism of TIM-dependent adhesion of the Ebola virus to a cell. Through coarse grained modeling we show that longer TIM stalks adhere more easily as they can sample a larger area, thus offering a mechanistic interpretation of an experimental finding. Better mechanistic understanding can lead to therapeutic ideas for blocking adhesion.

Transient mechanical interactions between cells and viscoelastic extracellular matrix

Soft Matter ◽  
2021 ◽  
Author(s):  
Brandon Matthew Slater ◽  
Jing Li ◽  
Dhiraj Indana ◽  
Yihao Xie ◽  
Ovijit Chaudhuri ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Physiological Processes ◽  
Contractile Forces ◽  
Surrounding Extracellular Matrix

During various physiological processes, such as wound healing and cell migration, cells continuously interact mechanically with a surrounding extracellular matrix (ECM). Contractile forces generated by the actin cytoskeleton are transmitted...

scholarly journals Method to study cell migration under uniaxial compression

2017 ◽  
Vol 28 (6) ◽  
pp. 809-816 ◽  
Author(s):  
Nishit Srivastava ◽  
Robert R. Kay ◽  
Alexandre J. Kabla
Keyword(s):  
Cell Migration ◽  
Uniaxial Compression ◽  
Physical And Mechanical Properties ◽  
Accurate Information ◽  
Simple Method ◽  
Novel Device ◽  
The Matrix ◽  
A Cell ◽  
Extracellular Environment ◽  
Selection Of

The chemical, physical, and mechanical properties of the extracellular environment have a strong effect on cell migration. Aspects such as pore size or stiffness of the matrix influence the selection of the mechanism used by cells to propel themselves, including by pseudopods or blebbing. How a cell perceives its environment and how such a cue triggers a change in behavior are largely unknown, but mechanics is likely to be involved. Because mechanical conditions are often controlled by modifying the composition of the environment, separating chemical and physical contributions is difficult and requires multiple controls. Here we propose a simple method to impose a mechanical compression on individual cells without altering the composition of the matrix. Live imaging during compression provides accurate information about the cell's morphology and migratory phenotype. Using Dictyostelium as a model, we observe that a compression of the order of 500 Pa flattens the cells under gel by up to 50%. This uniaxial compression directly triggers a transition in the mode of migration from primarily pseudopodial to bleb driven in <30 s. This novel device is therefore capable of influencing cell migration in real time and offers a convenient approach with which to systematically study mechanotransduction in confined environments.

scholarly journals A Wound-Healing Assay Based on Ultraviolet Light Ablation

2016 ◽  
Vol 22 (1) ◽  
pp. 36-43 ◽  
Author(s):  
Shang-Ying Wu ◽  
Yung-Shin Sun ◽  
Kuan-Chen Cheng ◽  
Kai-Yin Lo
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Healing Process ◽  
Cell Monolayer ◽  
Wound Healing Process ◽  
Collective Cell Migration ◽  
Wound Healing Assay ◽  
Physiological Processes ◽  
Free Region ◽  
A Cell

Collective cell migration plays important roles in many physiological processes such as embryonic development, tissue repair, and angiogenesis. A “wound” occurs when epithelial cells are lost and/or damaged due to some external factors, and collective cell migration takes place in the following wound-healing process. To study this cellular behavior, various kinds of wound-healing assays are developed. In these assays, a “wound,” or a “cell-free region,” is created in a cell monolayer mechanically, chemically, optically, or electrically. These assays are useful tools in studying the effects of certain physical or chemical stimuli on the wound-healing process. Most of these methods have disadvantages such as creating wounds of different sizes or shapes, yielding batch-to-batch variation, and damaging the coating of the cell culture surface. In this study, we used ultraviolet (UV) lights to selectively kill cells and create a wound out of a cell monolayer. A comparison between the current assay and the traditional scratch assay was made, indicating that these two methods resulted in similar wound-healing rates. The advantages of this UV-created wound-healing assay include fast and easy procedure, high throughput, and no direct contact to cells.

scholarly journals Understanding sex differences in long-term blood pressure regulation: insights from experimental studies and computational modeling

2019 ◽  
Vol 316 (5) ◽  
pp. H1113-H1123 ◽  
Author(s):  
Sameed Ahmed ◽  
Rui Hu ◽  
Jessica Leete ◽  
Anita T. Layton
Keyword(s):  
Blood Pressure ◽  
Sex Differences ◽  
Computational Models ◽  
Experimental Studies ◽  
Pressure Control ◽  
Blood Pressure Regulation ◽  
Pressure Regulation ◽  
Physiological Processes ◽  
Key Players

Sex differences in blood pressure and the prevalence of hypertension are found in humans and animal models. Moreover, there has been a recent explosion of data concerning sex differences in nitric oxide, the renin-angiotensin-aldosterone system, inflammation, and kidney function. These data have the potential to reveal the mechanisms underlying male-female differences in blood pressure control. To elucidate the interactions among the multitude of physiological processes involved, one may apply computational models. In this review, we describe published computational models that represent key players in blood pressure regulation, and highlight sex-specific models and their findings.

scholarly journals Enhanced Piezoelectric Fibered Extracellular Matrix to Promote Cardiomyocyte Maturation and Tissue Formation: A 3D Computational Model

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 135
Author(s):  
Pau Urdeitx ◽  
Mohamed H. Doweidar
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Computational Models ◽  
Cell Junctions ◽  
Tissue Formation ◽  
Cardiac Muscle Cells ◽  
Cell Processes ◽  
Electrical Stimuli ◽  
Cell Cell

Mechanical and electrical stimuli play a key role in tissue formation, guiding cell processes such as cell migration, differentiation, maturation, and apoptosis. Monitoring and controlling these stimuli on in vitro experiments is not straightforward due to the coupling of these different stimuli. In addition, active and reciprocal cell–cell and cell–extracellular matrix interactions are essential to be considered during formation of complex tissue such as myocardial tissue. In this sense, computational models can offer new perspectives and key information on the cell microenvironment. Thus, we present a new computational 3D model, based on the Finite Element Method, where a complex extracellular matrix with piezoelectric properties interacts with cardiac muscle cells during the first steps of tissue formation. This model includes collective behavior and cell processes such as cell migration, maturation, differentiation, proliferation, and apoptosis. The model has employed to study the initial stages of in vitro cardiac aggregate formation, considering cell–cell junctions, under different extracellular matrix configurations. Three different cases have been purposed to evaluate cell behavior in fibered, mechanically stimulated fibered, and mechanically stimulated piezoelectric fibered extra-cellular matrix. In this last case, the cells are guided by the coupling of mechanical and electrical stimuli. Accordingly, the obtained results show the formation of more elongated groups and enhancement in cell proliferation.

scholarly journals DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yixin Tong ◽  
Yuan Huang ◽  
Yuchao Zhang ◽  
Xiangtai Zeng ◽  
Mei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Downstream Target ◽  
Normal Tissues ◽  
Physiological Processes ◽  
Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

scholarly journals Power Failure of Mitochondria and Oxidative Stress in Neurodegeneration and Its Computational Models

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 229
Author(s):  
JunHyuk Woo ◽  
Hyesun Cho ◽  
YunHee Seol ◽  
Soon Ho Kim ◽  
Chanhyeok Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Computational Models ◽  
Neuronal Damage ◽  
Living Organism ◽  
The Body ◽  
Mitochondrial Functions ◽  
A Cell ◽  
The Brain ◽  
And Oxidative Stress

The brain needs more energy than other organs in the body. Mitochondria are the generator of vital power in the living organism. Not only do mitochondria sense signals from the outside of a cell, but they also orchestrate the cascade of subcellular events by supplying adenosine-5′-triphosphate (ATP), the biochemical energy. It is known that impaired mitochondrial function and oxidative stress contribute or lead to neuronal damage and degeneration of the brain. This mini-review focuses on addressing how mitochondrial dysfunction and oxidative stress are associated with the pathogenesis of neurodegenerative disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. In addition, we discuss state-of-the-art computational models of mitochondrial functions in relation to oxidative stress and neurodegeneration. Together, a better understanding of brain disease-specific mitochondrial dysfunction and oxidative stress can pave the way to developing antioxidant therapeutic strategies to ameliorate neuronal activity and prevent neurodegeneration.

Structure and Hardness of Cryorolled and Heat-Treated 2xxx Aluminum Alloy

2010 ◽  
Vol 667-669 ◽  
pp. 925-930
Author(s):  
S.V. Krymskiy ◽  
Elena Avtokratova ◽  
M.V. Markushev ◽  
Maxim Yu. Murashkin ◽  
O.S. Sitdikov
Keyword(s):  
Heat Treatment ◽  
Solid Solution ◽  
Plastic Deformation ◽  
Aluminum Alloy ◽  
Severe Plastic Deformation ◽  
Coarse Grained ◽  
Aging Response ◽  
Heat Treated ◽  
Aluminum Solid Solution ◽  
A Cell

The effects of severe plastic deformation (SPD) by isothermal rolling at the temperature of liquid nitrogen combined with prior- and post-SPD heat treatment, on microstructure and hardness of Al-4.4%Cu-1.4%Mg-0.7%Mn (D16) alloy were investigated. It was found no nanostructuring even after straining to 75%. Сryodeformation leads to microshear banding and processing the high-density dislocation substructures with a cell size of ~ 100-200 nm. Such a structure remains almost stable under 1 hr annealing up to 200oC and with further temperature increase initially transforms to bimodal with a small fraction of nanograins and then to uniform coarse grained one. It is found the change in the alloy post–SPD aging response leading to more active decomposition of the preliminary supersaturated aluminum solid solution, and to the alloy extra hardening under aging with shorter times and at lower temperatures compared to T6 temper.

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