scholarly journals Dynamic cellular finite-element method for modelling large-scale cell migration and proliferation under the control of mechanical and biochemical cues: a study of re-epithelialization

2017 ◽  
Vol 14 (129) ◽  
pp. 20160959 ◽  
Author(s):  
Jieling Zhao ◽  
Youfang Cao ◽  
Luisa A. DiPietro ◽  
Jie Liang
Keyword(s):  
Finite Element ◽  
Cell Migration ◽  
Large Scale ◽  
Full Range ◽  
Large Population ◽  
Computational Modelling ◽  
Cellular Protein ◽  
Collective Cell Migration ◽  
Cell Shapes ◽  
Cell Migration And Proliferation

Computational modelling of cells can reveal insight into the mechanisms of the important processes of tissue development. However, current cell models have limitations and are challenged to model detailed changes in cellular shapes and physical mechanics when thousands of migrating and interacting cells need to be modelled. Here we describe a novel dynamic cellular finite-element model (DyCelFEM), which accounts for changes in cellular shapes and mechanics. It also models the full range of cell motion, from movements of individual cells to collective cell migrations. The transmission of mechanical forces regulated by intercellular adhesions and their ruptures are also accounted for. Intra-cellular protein signalling networks controlling cell behaviours are embedded in individual cells. We employ DyCelFEM to examine specific effects of biochemical and mechanical cues in regulating cell migration and proliferation, and in controlling tissue patterning using a simplified re-epithelialization model of wound tissue. Our results suggest that biochemical cues are better at guiding cell migration with improved directionality and persistence, while mechanical cues are better at coordinating collective cell migration. Overall, DyCelFEM can be used to study developmental processes when a large population of migrating cells under mechanical and biochemical controls experience complex changes in cell shapes and mechanics.

scholarly journals Inferring parameters for a lattice-free model of cell migration and proliferation using experimental data

2017 ◽  
Author(s):  
Alexander P. Browning ◽  
Scott W. McCue ◽  
Rachelle N. Binny ◽  
Michael J. Plank ◽  
Esha T. Shah ◽  
...  
Keyword(s):  
Experimental Data ◽  
Cell Migration ◽  
Spatial Clustering ◽  
Cancer Cell Line ◽  
Movement Direction ◽  
Data Sets ◽  
Collective Cell Migration ◽  
Rejection Sampling ◽  
Data Set ◽  
Cell Migration And Proliferation

AbstractCollective cell spreading takes place in spatially continuous environments, yet it is often modelled using discrete lattice-based approaches. Here, we use data from a series of cell proliferation assays, with a prostate cancer cell line, to calibrate a spatially continuous individual based model (IBM) of collective cell migration and proliferation. The IBM explicitly accounts for crowding effects by modifying the rate of movement, direction of movement, and the rate of proliferation by accounting for pair-wise interactions. Taking a Bayesian approach we estimate the free parameters in the IBM using rejection sampling on three separate, independent experimental data sets. Since the posterior distributions for each experiment are similar, we perform simulations with parameters sampled from a new posterior distribution generated by combining the three data sets. To explore the predictive power of the calibrated IBM, we forecast the evolution of a fourth experimental data set. Overall, we show how to calibrate a lattice-free IBM to experimental data, and our work highlights the importance of interactions between individuals. Despite great care taken to distribute cells as uniformly as possible experimentally, we find evidence of significant spatial clustering over short distances, suggesting that standard mean-field models could be inappropriate.

scholarly journals The interplay of cell–cell and cell–substrate adhesion in collective cell migration

2014 ◽  
Vol 11 (100) ◽  
pp. 20140684 ◽  
Author(s):  
Chenlu Wang ◽  
Sagar Chowdhury ◽  
Meghan Driscoll ◽  
Carole A. Parent ◽  
S. K. Gupta ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Surface ◽  
Actin Polymerization ◽  
Collective Cell Migration ◽  
Cell Contacts ◽  
Substrate Adhesion ◽  
Cell Substrate ◽  
Cell Shapes ◽  
Cell Substrate Adhesion ◽  
Cell Cell

Collective cell migration often involves notable cell–cell and cell–substrate adhesions and highly coordinated motion of touching cells. We focus on the interplay between cell–substrate adhesion and cell–cell adhesion. We show that the loss of cell-surface contact does not significantly alter the dynamic pattern of protrusions and retractions of fast migrating amoeboid cells ( Dictyostelium discoideum ), but significantly changes their ability to adhere to other cells. Analysis of the dynamics of cell shapes reveals that cells that are adherent to a surface may coordinate their motion with neighbouring cells through protrusion waves that travel across cell–cell contacts. However, while shape waves exist if cells are detached from surfaces, they do not couple cell to cell. In addition, our investigation of actin polymerization indicates that loss of cell-surface adhesion changes actin polymerization at cell–cell contacts. To further investigate cell–cell/cell–substrate interactions, we used optical micromanipulation to form cell–substrate contact at controlled locations. We find that both cell-shape dynamics and cytoskeletal activity respond rapidly to the formation of cell–substrate contact.

scholarly journals A Dynamic Finite Element Cellular Model and Its Application on Cell Migration

2020 ◽  
Author(s):  
Jieling Zhao
Keyword(s):  
Finite Element ◽  
Cell Migration ◽  
Viscoelastic Model ◽  
Collective Cell Migration ◽  
Cellular Model ◽  
Cell Substrate ◽  
Epithelial Wound Healing ◽  
Triangular Elements ◽  
Intercellular Adhesions ◽  
Subcellular Level

While the tissue is formed or regenerated, cells migrate collectively and remained adherent. However, it is still unclear what are the roles of cell-substrate and intercellular interactions in regulating collective cell migration. In this chapter, we introduce our newly developed finite element cellular model to simulate the collective cell migration and explore the effects of mechanical feedback between cells and between cell and substrate. Our viscoelastic model represents one cell with many triangular elements. Intercellular adhesions between cells are represented as linear springs. Furthermore, we include a mechano-chemical feedback loop between cell-substrate mechanics and cell migration. Our results reproduce a set of experimental observation of patterns of collective cell migration during epithelial wound healing. In addition, we demonstrate that cell-substrate determined mechanics play an important role in regulating persistent and oriented collective cell migration. This chapter illustrates that our finite element cellular model can be applied to study a number of tissue related problems regarding cellular dynamic changes at subcellular level.

scholarly journals Enhancement of endothelialization by topographical features is mediated by PTP1B-dependent endothelial adherens junctions remodeling

2019 ◽  
Author(s):  
Azita Gorji ◽  
Pearlyn Jia Ying Toh ◽  
Yi-Chin Toh ◽  
Yusuke Toyama ◽  
Pakorn Kanchanawong
Keyword(s):  
Cell Migration ◽  
Adherens Junctions ◽  
Tyrosine Phosphatase ◽  
Inhibitory Effect ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Combined Strategy ◽  
Cell Migration And Proliferation ◽  
Arterial Endothelial Cells ◽  
Cell Cell

RationaleFailure of small synthetic vascular grafts is largely due to late endothelialization and has been an ongoing challenge in the treatment of cardiovascular diseases.ObjectivePrevious strategies developed to promote graft endothelialization include surface topographical modulation and biochemical modifications. However, these have been met with limited success. Importantly, although the integrity of Endothelial Cell (EC) monolayer is crucial for endothelialization, the crosstalk between surface topography and cell-cell connectivity is still not well understood. Here we explored a combined strategy that utilizes both topographical features and pharmacological perturbations.Methods and resultWe characterized EC behaviors in response to micron-scale grating topography in conjunction with pharmacological perturbations of endothelial adherens junctions (EAJ) regulators. We studied the EA.hy 926 cell-cell junctions and monolayer integrity using the junctional markers upon the inhibitory effect of EAJ regulator on both planar and grating topographies substrates.We identified a protein tyrosine phosphatase, PTP1B, as a potent regulator of EAJ stability. Next, we studied the physiologically relevant behaviors of EC using primary human coronary arterial endothelial cells (HCAEC). Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration to promote endothelialization.Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration and proliferation.ConclusionThe synergistic effect of PTP1B inhibition and grating topographies could be useful for the promotion of endothelialization by enhancing EC migration and proliferation.

scholarly journals Emergence of single cell mechanical behavior and polarity within epithelial monolayers drives collective cell migration

2019 ◽  
Author(s):  
Shreyansh Jain ◽  
Victoire M.L. Cachoux ◽  
Gautham H.N.S. Narayana ◽  
Simon de Beco ◽  
Joseph D’Alessandro ◽  
...  
Keyword(s):  
Cell Migration ◽  
Single Cell ◽  
Large Scale ◽  
Cancer Metastasis ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Convergent Extension ◽  
Cell Dynamics

The directed migration of cell collectives is essential in various physiological processes, such as epiboly, intestinal epithelial turnover, and convergent extension during morphogenesis as well as during pathological events like wound healing and cancer metastasis1,2. Collective cell migration leads to the emergence of coordinated movements over multiple cells. Our current understanding emphasizes that these movements are mainly driven by large-scale transmission of signals through adherens junctions3,4. In this study, we show that collective movements of epithelial cells can be triggered by polarity signals at the single cell level through the establishment of coordinated lamellipodial protrusions. We designed a minimalistic model system to generate one-dimensional epithelial trains confined in ring shaped patterns that recapitulate rotational movements observed in vitro in cellular monolayers and in vivo in genitalia or follicular cell rotation5–7. Using our system, we demonstrated that cells follow coordinated rotational movements after the establishment of directed Rac1-dependent polarity over the entire monolayer. Our experimental and numerical approaches show that the maintenance of coordinated migration requires the acquisition of a front-back polarity within each single cell but does not require the maintenance of cell-cell junctions. Taken together, these unexpected findings demonstrate that collective cell dynamics in closed environments as observed in multiple in vitro and in vivo situations5,6,8,9 can arise from single cell behavior through a sustained memory of cell polarity.

scholarly journals Mechanocellular models of epithelial morphogenesis

2017 ◽  
Vol 372 (1720) ◽  
pp. 20150519 ◽  
Author(s):  
Alexander G. Fletcher ◽  
Fergus Cooper ◽  
Ruth E. Baker
Keyword(s):  
Large Scale ◽  
Computational Models ◽  
Computational Modelling ◽  
Tissue Level ◽  
Epithelial Morphogenesis ◽  
Immersed Boundary ◽  
Finite Element Models ◽  
Cell Shapes ◽  
Technical Advances ◽  
Experimental Approaches

Embryonic epithelia achieve complex morphogenetic movements, including in-plane reshaping, bending and folding, through the coordinated action and rearrangement of individual cells. Technical advances in molecular and live-imaging studies of epithelial dynamics provide a very real opportunity to understand how cell-level processes facilitate these large-scale tissue rearrangements. However, the large datasets that we are now able to generate require careful interpretation. In combination with experimental approaches, computational modelling allows us to challenge and refine our current understanding of epithelial morphogenesis and to explore experimentally intractable questions. To this end, a variety of cell-based modelling approaches have been developed to describe cell–cell mechanical interactions, ranging from vertex and ‘finite-element’ models that approximate each cell geometrically by a polygon representing the cell's membrane, to immersed boundary and subcellular element models that allow for more arbitrary cell shapes. Here, we review how these models have been used to provide insights into epithelial morphogenesis and describe how such models could help future efforts to decipher the forces and mechanical and biochemical feedbacks that guide cell and tissue-level behaviour. In addition, we discuss current challenges associated with using computational models of morphogenetic processes in a quantitative and predictive way. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’.

Numerical Simulation of Tire Sliding Events Involving Impacts with Holes and Bumps

1986 ◽  
Vol 14 (2) ◽  
pp. 125-136 ◽  
Author(s):  
Y. Nakajima ◽  
J. Padovan
Keyword(s):  
Numerical Simulation ◽  
Finite Element ◽  
Finite Element Simulation ◽  
Full Range ◽  
Arbitrary Geometry ◽  
Operating Environments ◽  
Element Simulation ◽  
Simulation Scheme

Abstract This paper extends the finite element simulation scheme to handle the problem of tires undergoing sliding (skidding) impact into obstructions. Since the inertial characteristics are handled by the algorithm developed, the full range of operating environments can be accommodated. This includes the treatment of impacts with holes and bumps of arbitrary geometry.

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