scholarly journals Combinative in vitro studies and computational model to predict 3D cell migration response to drug insult

2014 ◽  
Vol 6 (10) ◽  
pp. 957-972 ◽  
Author(s):  
Joseph S. Maffei ◽  
Jaya Srivastava ◽  
Brian Fallica ◽  
Muhammad H. Zaman
Keyword(s):  
Cell Migration ◽  
Computational Model ◽  
In Vitro Studies ◽  
3D Cell Migration ◽  
Migration Response

scholarly journals Developmental Neurotoxicity of Fipronil and Rotenone on a Human Neuronal In Vitro Test System

2021 ◽  
Author(s):  
Anne Schmitz ◽  
Silke Dempewolf ◽  
Saime Tan ◽  
Gerd Bicker ◽  
Michael Stern
Keyword(s):  
Cell Migration ◽  
Neurite Outgrowth ◽  
Neuronal Differentiation ◽  
Precursor Cell ◽  
Developmental Neurotoxicity ◽  
In Vitro Studies ◽  
Human Model ◽  
In Vitro Test ◽  
Dependent Manner

AbstractPesticide exposure during in utero and early postnatal development can cause a wide range of neurological defects. However, relatively few insecticides have been recognized as developmental neurotoxicants, so far. Recently, discovery of the insecticide, fipronil, in chicken eggs has raised public concern. The status of fipronil as a potential developmental neurotoxicant is still under debate. Whereas several in vivo and in vitro studies suggest specific toxicity, other in vitro studies could not confirm this concern. Here, we tested fipronil and its main metabolic product, fipronil sulfone both at concentrations between 1.98 and 62.5 µM, alongside with the established developmental neurotoxicant, rotenone (0.004–10 µM) in vitro on the human neuronal precursor cell line NT2. We found that rotenone impaired all three tested DNT endpoints, neurite outgrowth, neuronal differentiation, and precursor cell migration in a dose-dependent manner and clearly separable from general cytotoxicity in the nanomolar range. Fipronil and fipronil sulfone specifically inhibited cell migration and neuronal differentiation, but not neurite outgrowth in the micromolar range. The rho-kinase inhibitor Y-27632 counteracted inhibition of migration for all three compounds (EC50 between 12 and 50 µM). The antioxidant, n-acetyl cysteine, could ameliorate the inhibitory effects of fipronil on all three tested endpoints (EC 50 between 84 and 164 µM), indicating the involvement of oxidative stress. Fipronil sulfone had a stronger effect than fipronil, confirming the importance to test metabolic products alongside original pesticides. We conclude that in vitro fipronil and fipronil sulfone display specific developmental neurotoxicity on developing human model neurons.

scholarly journals The Effect of Microfluidic Geometry on Myoblast Migration

Micromachines ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 143
Author(s):  
Rahul Atmaramani ◽  
Bryan Black ◽  
Kevin Lam ◽  
Vinit Sheth ◽  
Joseph Pancrazio ◽  
...  
Keyword(s):  
Cell Migration ◽  
Microfluidic Devices ◽  
In Vitro Studies ◽  
Future Design ◽  
The Future ◽  
Pdms Microchannel ◽  
In Vitro Systems ◽  
Spontaneous Migration ◽  
Over Time

In vitro systems comprised of wells interconnected by microchannels have emerged as a platform for the study of cell migration or multicellular models. In the present study, we systematically evaluated the effect of microchannel width on spontaneous myoblast migration across these microchannels—from the proximal to the distal chamber. Myoblast migration was examined in microfluidic devices with varying microchannel widths of 1.5–20 µm, and in chips with uniform microchannel widths over time spans that are relevant for myoblast-to-myofiber differentiation in vitro. We found that the likelihood of spontaneous myoblast migration was microchannel width dependent and that a width of 3 µm was necessary to limit spontaneous migration below 5% of cells in the seeded well after 48 h. These results inform the future design of Polydimethylsiloxane (PDMS) microchannel-based co-culture platforms as well as future in vitro studies of myoblast migration.

scholarly journals Computational model of 3D cell migration based on the molecular clutch mechanism

2021 ◽  
Author(s):  
Samuel Campbell ◽  
Rebecca Zitnay ◽  
Michelle Mendoza ◽  
Tamara C Bidone
Keyword(s):  
Cell Migration ◽  
Computational Model ◽  
Cell Activity ◽  
Cell Replication ◽  
Cell Contractility ◽  
Matrix Microstructure ◽  
The Matrix ◽  
Mechanical Factors ◽  
Clutch Mechanism ◽  
3D Cell Migration

AbstractThe external environment is a regulator of cell activity. Its stiffness and microstructure can either facilitate or prevent 3D cell migration in both physiology and disease. 3D cell migration results from force feedbacks between the cell and the extracellular matrix (ECM). Adhesions regulate these force feedbacks by working as molecular clutches that dynamically bind and unbind the ECM. Because of the interdependency between ECM properties, adhesion dynamics, and cell contractility, how exactly 3D cell migration occurs in different environments is not fully understood. In order to elucidate the effect of ECM on 3D cell migration through force-sensitive molecular clutches, we developed a computational model based on a lattice point approach. Results from the model show that increases in ECM pore size reduce cell migration speed. In contrast, matrix porosity increases it, given a sufficient number of ligands for cell adhesions and limited crowding of the matrix from cell replication. Importantly, these effects are maintained across a range of ECM stiffnesses’, demonstrating that mechanical factors are not responsible for how matrix microstructure regulates cell motility.

scholarly journals The role of actin protrusion dynamics in cell migration through a degradable viscoelastic extracellular matrix: Insights from a computational model

2019 ◽  
Author(s):  
Tommy Heck ◽  
Diego A. Vargas ◽  
Bart Smeets ◽  
Herman Ramon ◽  
Paul Van Liedekerke ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Computational Model ◽  
Mechanical Anisotropy ◽  
Valuable Contribution ◽  
Anisotropic Mechanical Properties ◽  
Subcellular Processes ◽  
3D Cell Migration ◽  
Cell Strength

AbstractActin protrusion dynamics plays an important role in the regulation of three-dimensional (3D) cell migration. Cells form protrusions that adhere to the surrounding extracellular matrix (ECM), mechanically probe the ECM and contract in order to displace the cell body. This results in cell migration that can be directed by the mechanical anisotropy of the ECM. However, the subcellular processes that regulate protrusion dynamics in 3D cell migration are difficult to investigate experimentally and therefore not well understood. Here, we present a computational model of cell migration through a degradable viscoelastic ECM. The cell is modeled as an active deformable object that captures the viscoelastic behavior of the actin cortex and the subcellular processes underlying 3D cell migration. The ECM is regarded as a viscoelastic material, with or without anisotropy due to fibrillar strain stiffening, and modeled by means of the meshless Lagrangian smoothed particle hydrodynamics (SPH) method. ECM degradation is captured by local fluidization of the material and permits cell migration through the ECM. We demonstrate that changes in ECM stiffness and cell strength affect cell migration and are accompanied by changes in number, lifetime and length of protrusions. Interestingly, directly changing the total protrusion number or the average lifetime or length of protrusions does not affect cell migration. A stochastic variability in protrusion lifetime proves to be enough to explain differences in cell migration velocity. Force-dependent adhesion disassembly does not result in faster migration, but can make migration more efficient. We also demonstrate that when a number of simultaneous protrusions is enforced, the optimal number of simultaneous protrusions is one or two, depending on ECM anisotropy. Together, the model provides non-trivial new insights in the role of protrusions in 3D cell migration and can be a valuable contribution to increase the understanding of 3D cell migration mechanics.Author summaryThe ability of cells to migrate through a tissue in the human body is vital for many processes such as tissue development, growth and regeneration. At the same time, abnormal cell migration is also playing an important role in many diseases such as cancer. If we want to be able to explain the origin of these abnormalities and develop new treatment strategies, we have to understand how cells are able to regulate their migration. Since it is challenging to investigate cell migration through a biological tissue in experiments, computational modeling can provide a valuable contribution. We have developed a computational model of cell migration through a deformable and degradable material that describes both mechanics of the cell and the surrounding material and subcellular processes underlying cell migration. This model captures the formation of long and thin protrusions that adhere to the surrounding material and that pull the cell forward. It provides new non-trivial insights in the role of these protrusions in cell migration and the regulation of protrusion dynamics by cell strength and anisotropic mechanical properties of the surrounding material. Therefore, we believe that this model can be a valuable tool to further improve the understanding of cell migration.

scholarly journals Integration of in vitro and in silico Models Using Bayesian Optimization With an Application to Stochastic Modeling of Mesenchymal 3D Cell Migration

2018 ◽  
Vol 9 ◽  
Author(s):  
Francisco Merino-Casallo ◽  
Maria J. Gomez-Benito ◽  
Yago Juste-Lanas ◽  
Ruben Martinez-Cantin ◽  
Jose M. Garcia-Aznar
Keyword(s):  
Cell Migration ◽  
Stochastic Modeling ◽  
In Silico ◽  
Bayesian Optimization ◽  
3D Cell Migration ◽  
In Silico Models

scholarly journals Generation of fluorescent cell-derived-matrix to study 3D cell migration

2019 ◽  
Author(s):  
Amélie Luise Godeau ◽  
Hélène Delanoë-Ayari ◽  
Daniel Riveline
Keyword(s):  
Cell Migration ◽  
Flat Surfaces ◽  
Polymeric Networks ◽  
Motile Cells ◽  
Matrix Deformation ◽  
3D Cell Migration ◽  
Cell Motion ◽  
Cellular Forces

AbstractCell migration is involved in key phenomena in biology, ranging from development to cancer. Fibroblasts move between organs in 3D polymeric networks. So far, motile cells were mainly tracked in vitro on Petri dishes or on coverslips, i.e. 2D flat surfaces, which made the extrapolation to 3D physiological environments difficult. We therefore prepared 3D Cell Derived Matrix (CDM) with specific characteristics with the goal of extracting the main readouts required to measure and characterise cell motion: cell specific matrix deformation through the tracking of fluorescent fibronectin within CDM, focal contacts as the cell anchor and acto-myosin cytoskeleton which applies cellular forces. We report our method for generating this assay of physiological-like gel with relevant readouts together with its potential impact in explaining cell motility in vivo.

The Role of Integrin αDβ2 in Macrophage Migration.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2215-2215
Author(s):  
Valentin P. Yakubenko ◽  
Tatiana P. Ugarova
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Extracellular Matrix Proteins ◽  
In Vitro Studies ◽  
Matrix Proteins ◽  
Hek293 Cells ◽  
Macrophage Migration ◽  
Blocking Antibodies

Abstract Integrin αDβ2 (CD11d/CD18), the most recently discovered member of the β2 sub-family of adhesion receptors, is strongly upregulated on macrophage foam cells which underscores its potential role in atherosclerosis. However, the contribution of αDβ2 to monocyte/macrophage adhesive reactions and the significance of its overexpression on these cells remain unknown. Recently we characterized αDβ2 as a multiligand receptor capable of binding many extracellular matrix proteins with the recognition specificity overlapping that of the major myeloid-specific integrin αMβ2 (Mac-1). We hypothesized that the αDβ2 ability to bind numerous ligands in the extracellular matrix and its capacity to be upregulated to high density on the surface of macrophages may modulate cell adhesiveness and, thus, affect migration. To evaluate the role of αDβ2 in migration, we generated model and natural cells expressing different densities of αDβ2 and tested their migration to different extracellular matrix proteins. In vitro studies demonstrated that αDβ2 expressed at low densities, either on the surface of HEK293 cells or the mouse macrophage cell line IC-21, supported migration which was partially inhibited by anti-αD function-blocking antibodies. Furthermore, β1 and β3 integrins expressed on HEK293 cells and IC-21 macrophages, respectively, contributed to migration because anti-β1 and anti-β3 antibodies inhibited migration. Increased expression of αDβ2 on the surface of HEK293 cells and its upregulation by PMA on IC-21 macrophages resulted in the inhibition of cell migration. Ligation of αDβ2 with anti-αD antibodies restored β1- and β3-driven cell migration by means of removing restraints imposed by the excess of the αDβ2-ligand adhesive bonds. To test the possibility that progressive upregulation of αDβ2 can block macrophage migration in vivo, we assessed the effect of anti-αD function blocking antibodies using the thioglycollate-induced peritonitis model. More than 4-fold upregulation of αDβ2 was detected on macrophages in 72 h after thioglycollate stimulation and, similar to in vitro studies, the numbers of migration macrophages increased in the presence of anti-αD antibodies. These results demonstrate that the density of αDβ2 can modulate cell migration and suggest that low levels of αDβ2 can contribute to monocyte migration while αDβ2 upregulation on differentiated macrophages might facilitate their retention at the site of inflammation.

scholarly journals Guiding 3D cell migration in deformed synthetic hydrogel microstructures

Soft Matter ◽  
2018 ◽  
Vol 14 (15) ◽  
pp. 2816-2826 ◽  
Author(s):  
Miriam Dietrich ◽  
Hugo Le Roy ◽  
David B. Brückner ◽  
Hanna Engelke ◽  
Roman Zantl ◽  
...  
Keyword(s):  
Cell Migration ◽  
Theoretical Modelling ◽  
Synthetic Hydrogel ◽  
3D Cell Migration ◽  
External Strain ◽  
Migration Response

In this study we combine experiments and theoretical modelling to analyse the anisotropic migration response of cells to external strain.

Neutrophil migration through in vitro interstitial matrix

1992 ◽  
Vol 50 (1) ◽  
pp. 894-895
Author(s):  
J. Roemer ◽  
S.R. Simon
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Inflammatory Cell ◽  
Neutrophil Migration ◽  
Culture Conditions ◽  
Aortic Smooth Muscle ◽  
Specific Culture

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

In vitro - studies with antler bone cells: Structure forming capacity, osteocalcin production and influence of sex steroids

2006 ◽  
Vol 15 (04) ◽  
pp. 245-257 ◽  
Author(s):  
H. J. Rolf ◽  
K. G. Wiese ◽  
H. Siggelkow ◽  
H. Schliephake ◽  
G. A. Bubernik
Keyword(s):  
Sex Steroids ◽  
Bone Cells ◽  
In Vitro Studies ◽  
Osteocalcin Production
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