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 Tuning cell migration: contractility as an integrator of intracellular signals from multiple cues

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1819 ◽  
Author(s):  
Francois Bordeleau ◽  
Cynthia A. Reinhart-King
Keyword(s):  
Cell Migration ◽  
Growth Factors ◽  
Three Dimensional ◽  
Two Dimensional ◽  
Multiple Cues ◽  
Cell Contractility ◽  
Cell Matrix ◽  
Intracellular Signals ◽  
Physical Cues ◽  
The Matrix

There has been immense progress in our understanding of the factors driving cell migration in both two-dimensional and three-dimensional microenvironments over the years. However, it is becoming increasingly evident that even though most cells share many of the same signaling molecules, they rarely respond in the same way to migration cues. To add to the complexity, cells are generally exposed to multiple cues simultaneously, in the form of growth factors and/or physical cues from the matrix. Understanding the mechanisms that modulate the intracellular signals triggered by multiple cues remains a challenge. Here, we will focus on the molecular mechanism involved in modulating cell migration, with a specific focus on how cell contractility can mediate the crosstalk between signaling initiated at cell-matrix adhesions and growth factor receptors.

scholarly journals Nascent adhesions differentially regulate lamellipodium velocity and persistence

2021 ◽  
Author(s):  
Keith R Carney ◽  
Akib M Khan ◽  
Shiela C Samson ◽  
Nikhil Mittal ◽  
Sangyoon J Han ◽  
...  
Keyword(s):  
Cell Migration ◽  
Computational Model ◽  
Actin Filament ◽  
Actin Polymerization ◽  
Leading Edge ◽  
Membrane Tension ◽  
Cell Edge ◽  
Ratchet Mechanism ◽  
Model Predictions ◽  
Clutch Mechanism

Cell migration is essential to physiological and pathological biology. Migration is driven by the motion of a leading edge, in which actin polymerization pushes against the edge and adhesions transmit traction to the substrate while membrane tension increases. How the actin and adhesions synergistically control edge protrusion remains elusive. We addressed this question by developing a computational model in which the Brownian ratchet mechanism governs actin filament polymerization against the membrane and the molecular clutch mechanism governs adhesion to the substrate (BR-MC model). Our model predicted that actin polymerization is the most significant driver of protrusion, as actin had a greater effect on protrusion than adhesion assembly. Increasing the lifetime of nascent adhesions also enhanced velocity, but decreased the protrusion's motional persistence, because filaments maintained against the cell edge ceased polymerizing as membrane tension increased. We confirmed the model predictions with measurement of adhesion lifetime and edge motion in migrating cells. Adhesions with longer lifetime were associated with faster protrusion velocity and shorter persistence. Experimentally increasing adhesion lifetime increased velocity but decreased persistence. We propose a mechanism for actin polymerization-driven, adhesion-dependent protrusion in which balanced nascent adhesion assembly and lifetime generates protrusions with the power and persistence to drive migration.

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 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

Effect of matrix microstructure on the matrix/M2B wear interaction and its quantitative characterization in an Fe-2wt%B alloy

Wear ◽  
2021 ◽  
Vol 472-473 ◽  
pp. 203608
Author(s):  
Yanliang Yi ◽  
Qiang Li ◽  
Shaolei Long ◽  
Zhen Lv ◽  
Shuangjian Li ◽  
...  
Keyword(s):  
Quantitative Characterization ◽  
Matrix Microstructure ◽  
The Matrix

scholarly journals Computational Model for Cell Migration in Three-Dimensional Matrices

2005 ◽  
Vol 89 (2) ◽  
pp. 1389-1397 ◽  
Author(s):  
Muhammad H. Zaman ◽  
Roger D. Kamm ◽  
Paul Matsudaira ◽  
Douglas A. Lauffenburger
Keyword(s):  
Cell Migration ◽  
Computational Model ◽  
Three Dimensional

scholarly journals Senescent stromal cells induce cancer cell migration via inhibition of RhoA/ROCK/myosin-based cell contractility

Oncotarget ◽  
2015 ◽  
Vol 6 (31) ◽  
pp. 30516-30531 ◽  
Author(s):  
Ivie Aifuwa ◽  
Anjil Giri ◽  
Nick Longe ◽  
Sang Hyuk Lee ◽  
Steven S. An ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Cancer Cell Migration ◽  
Cell Contractility

scholarly journals EBSD Analysis of Metal Matrix Nanocomposite Microstructure Produced by Powder Metallurgy

Nanomaterials ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 878 ◽  
Author(s):  
Íris Carneiro ◽  
Filomena Viana ◽  
Manuel F. Vieira ◽  
José V. Fernandes ◽  
Sónia Simões
Keyword(s):  
Powder Metallurgy ◽  
Advanced Materials ◽  
Sintering Process ◽  
Electron Backscattered Diffraction ◽  
Matrix Microstructure ◽  
Metal Matrix Nanocomposite ◽  
The Matrix ◽  
Dislocation Annihilation ◽  
Metal Nanocomposites ◽  
Matrix Nanocomposite

The development of metal nanocomposites reinforced by carbon nanotubes (CNTs) remains a focus of the scientific community due to the growing need to produce lightweight advanced materials with unique mechanical properties. However, for the successful production of these nanocomposites, there is a need to consolidate knowledge about how reinforcement influences the matrix microstructure and which are the strengthening mechanisms promoting the best properties. In this context, this investigation focuses on the study of the reinforcement effect on the microstructure of an Ni-CNT nanocomposites produced by powder metallurgy. The microstructural evolution was analysed by electron backscattered diffraction (EBSD). The EBSD results revealed that the dispersion/mixing and pressing processes induce plastic deformation in the as-received powders. The dislocation structures produced in those initial steps are partially eliminated in the sintering process due to the activation of recovery and recrystallization mechanisms. However, the presence of CNTs in the matrix has a significant effect on the dislocation annihilation, thus reducing the recovery of the dislocation structures.

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