scholarly journals Active Vertex Model for Cell-Resolution Description of Epithelial Tissue Mechanics

2016 ◽  
Author(s):  
Daniel L. Barton ◽  
Silke Henkes ◽  
Cornelis J. Weijer ◽  
Rastko Sknepnek
Keyword(s):  
Multiple Scales ◽  
Tissue Mechanics ◽  
Epithelial Tissue ◽  
Vertex Model ◽  
Cell Alignment ◽  
Motion Patterns ◽  
Epithelial Tissues ◽  
Cell Motion ◽  
Natural Description ◽  
Active Vertex

We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.

scholarly journals Active Vertex Model for cell-resolution description of epithelial tissue mechanics

2017 ◽  
Vol 13 (6) ◽  
pp. e1005569 ◽  
Author(s):  
Daniel L. Barton ◽  
Silke Henkes ◽  
Cornelis J. Weijer ◽  
Rastko Sknepnek
Keyword(s):  
Tissue Mechanics ◽  
Epithelial Tissue ◽  
Vertex Model ◽  
Active Vertex

scholarly journals Glassy dynamics in models of confluent tissue with mitosis and apoptosis

Soft Matter ◽  
2019 ◽  
Vol 15 (44) ◽  
pp. 9133-9149 ◽  
Author(s):  
Michael Czajkowski ◽  
Daniel M. Sussman ◽  
M. Cristina Marchetti ◽  
M. Lisa Manning
Keyword(s):  
Cell Death ◽  
Life Cycle ◽  
Cell Division ◽  
Epithelial Tissue ◽  
Vertex Model ◽  
Glassy Dynamics ◽  
Cell Life ◽  
Active Vertex

Using a new Active Vertex Model of confluent epithelial tissue, we investigate the effect of cell division and cell death on previously identified glassy dynamics and establish how fast the cell life cycle must be in order to disrupt the observed dynamical signatures of glass-like behavior.

scholarly journals Motility induced fracture reveals a ductile to brittle crossover in the epithelial tissues of a simple animal

2019 ◽  
Author(s):  
Vivek N. Prakash ◽  
Matthew S. Bull ◽  
Manu Prakash
Keyword(s):  
Materials Science ◽  
Shape Change ◽  
Living Organism ◽  
Tissue Mechanics ◽  
Ecological Niches ◽  
Epithelial Tissue ◽  
Dynamic Force ◽  
Epithelial Tissues ◽  
Important Barrier ◽  
Rapid Healing

ABSTRACTAnimals are characterized by their movement, and their tissues are continuously subjected to dynamic force loading while they crawl, walk, run or swim1. Tissue mechanics fundamentally determine the ecological niches that can be endured by a living organism2. While epithelial tissues provide an important barrier function in animals, they are subjected to extreme strains during day to day physiological activities, such as breathing1, feeding3, and defense response4. How-ever, failure or inability to withstand to these extreme strains can result in epithelial fractures5, 6 and associated diseases7, 8. From a materials science perspective, how properties of living cells and their interactions prescribe larger scale tissue rheology and adaptive response in dynamic force landscapes remains an important frontier9. Motivated by pushing tissues to the limits of their integrity, we carry out a multi-modal study of a simple yet highly dynamic organism, the Trichoplax Adhaerens10–12, across four orders of magnitude in length (1 µm to 10 mm), and six orders in time (0.1 sec to 10 hours). We report the discovery of abrupt, bulk epithelial tissue fractures (∼10 sec) induced by the organism’s own motility. Coupled with rapid healing (∼10 min), this discovery accounts for dramatic shape change and physiological asexual division in this early-divergent metazoan. We generalize our understanding of this phenomena by codifying it in a heuristic model, highlighting the fundamental questions underlying the debonding/bonding criterion in a soft-active-living material by evoking the concept of an ‘epithelial alloy’. Using a suite of quantitative experimental and numerical techniques, we demonstrate a force-driven ductile to brittle material transition governing the morphodynamics of tissues pushed to the edge of rupture. This work contributes to an important discussion at the core of developmental biology13–17, with important applications to an emerging paradigm in materials and tissue engineering5, 18–20, wound healing and medicine8, 21, 22.

Epithelial Structural Proteins of the Skin and Oral Cavity: Function in Health and Disease

2000 ◽  
Vol 11 (4) ◽  
pp. 383-408 ◽  
Author(s):  
Richard B. Presland ◽  
Beverly A. Dale
Keyword(s):  
Target Genes ◽  
Three Dimensional ◽  
Epithelial Differentiation ◽  
Structural Proteins ◽  
Epithelial Tissue ◽  
Cell Integrity ◽  
Oral Keratinocytes ◽  
Differentiation Markers ◽  
Cornified Envelope ◽  
Epithelial Tissues

Epithelial tissues function to protect the organism from physical, chemical, and microbial damage and are essential for survival. To perform this role, epithelial keratinocytes undergo a well-defined differentiation program that results in the expression of structural proteins which maintain the integrity of epithelial tissues and function as a protective barrier. This review focuses on structural proteins of the epidermis and oral mucosa. Keratin proteins comprise the predominant cytoskeletal component of these epithelia. Keratin filaments are attached to the plasma membrane via desmosomes, and together these structural components form a three-dimensional array within the cytoplasm of epithelial cells and tissues. Desmosomes contain two types of transmembrane proteins, the desmogleins and desmocollins, that are members of the cadherin family. The desmosomal cadherins are linked to the keratin cytoskeleton via several cytoplasmic plaque proteins, including desmoplakin and plakoglobin (γ-catenin). Epidermal and oral keratinocytes express additional differentiation markers, including filaggrin and trichohyalin, that associate with the keratin cytoskeleton during terminal differentiation, and proteins such as loricrin, small proline-rich proteins, and involucrin, that are cross-linked into the cornified envelope by transglutaminase enzymes. The importance of these cellular structures is highlighted by the large numbers of genetic and acquired (autoimmune) human disorders that involve mutations in, or autoantibodies to, keratins and desmosomal and cornified envelope proteins. While much progress has been made in the identification of the structural proteins and enzymes involved in epithelial differentiation, regulation of this process is less clear. Both calcium and retinoids influence epithelial differentiation by altering the transcription of target genes and by regulating activity of enzymes critical in epithelial differentiation, such as transglutaminases proteinases, and protein kinases. These studies have furthered our understanding of how epithelial tissue and cell integrity is maintained and provide a basis for the future treatment of skin and oral disorders by gene therapy and other novel therapeutics

On Networks and Monsters: The Possible and the Actual in Complex Systems

Leonardo ◽  
2008 ◽  
Vol 41 (3) ◽  
pp. 253-258 ◽  
Author(s):  
Ricard Solé
Keyword(s):  
Complex Systems ◽  
Real World ◽  
Multiple Scales ◽  
Social Systems ◽  
Emergent Phenomena ◽  
Genome Dynamics ◽  
Natural Description

Complex systems pervade our real world, from social systems to genome dynamics. All these systems are characterized by the presence of emergent phenomena: New properties emerge from the interactions of simpler units and are not reducible to the properties of the latter. The natural description of complex systems involves a network view, where each system is represented by means of a web. Such graphs have been shown to share surprisingly universal patterns of organization, indicating that fundamental laws of organization also pervade complexity at multiple scales.

scholarly journals A modular framework for multiscale, multicellular, spatiotemporal modeling of acute primary viral infection and immune response in epithelial tissues and its application to drug therapy timing and effectiveness

2020 ◽  
Author(s):  
T.J. Sego ◽  
Josua O. Aponte-Serrano ◽  
Juliano Ferrari Gianlupi ◽  
Samuel R. Heaps ◽  
Kira Breithaupt ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Open Source ◽  
Tissue Damage ◽  
Rapid Development ◽  
Treatment Success ◽  
Epithelial Tissue ◽  
Parallel Development ◽  
Epithelial Tissues ◽  
Infection Mechanisms

AbstractSimulations of tissue-specific effects of primary acute viral infections like COVID-19 are essential for understanding disease outcomes and optimizing therapies. Such simulations need to support continuous updating in response to rapid advances in understanding of infection mechanisms, and parallel development of components by multiple groups. We present an open-source platform for multiscale spatiotemporal simulation of an epithelial tissue, viral infection, cellular immune response and tissue damage, specifically designed to be modular and extensible to support continuous updating and parallel development. The base simulation of a simplified patch of epithelial tissue and immune response exhibits distinct patterns of infection dynamics from widespread infection, to recurrence, to clearance. Slower viral internalization and faster immune-cell recruitment slow infection and promote containment. Because antiviral drugs can have side effects and show reduced clinical effectiveness when given later during infection, we studied the effects on progression of treatment potency and time-of-first treatment after infection. In simulations, even a low potency therapy with a drug which reduces the replication rate of viral RNA greatly decreases the total tissue damage and virus burden when given near the beginning of infection. Many combinations of dosage and treatment time lead to stochastic outcomes, with some simulation replicas showing clearance or control (treatment success), while others show rapid infection of all epithelial cells (treatment failure). Thus, while a high potency therapy usually is less effective when given later, treatments at late times are occasionally effective. We illustrate how to extend the platform to model specific virus types (e.g., hepatitis C) and add additional cellular mechanisms (tissue recovery and variable cell susceptibility to infection), using our software modules and publicly-available software repository.Author summaryThis study presents an open-source, extensible, multiscale platform for simulating viral immune interactions in epithelial tissues, which enables the rapid development and deployment of sophisticated models of viruses, infection mechanisms and tissue types. The model is used to investigate how potential treatments influence disease progression. Simulation results suggest that drugs which interfere with virus replication (e.g., remdesivir) yield substantially better infection outcomes when administered prophylactically even at very low doses than when used at high doses as treatment for an infection that has already begun.

scholarly journals Quantification of Cardiomyocyte Alignment from Three-Dimensional (3D) Confocal Microscopy of Engineered Tissue

2017 ◽  
Vol 23 (4) ◽  
pp. 826-842 ◽  
Author(s):  
William J. Kowalski ◽  
Fangping Yuan ◽  
Takeichiro Nakane ◽  
Hidetoshi Masumoto ◽  
Marc Dwenger ◽  
...  
Keyword(s):  
Multiple Scales ◽  
Orientational Order ◽  
Three Dimensional ◽  
Biological Tissues ◽  
Cardiac Cells ◽  
Cell Alignment ◽  
Cardiac Tissues ◽  
Automated Method ◽  
Synthetic Images ◽  
Induced Pluripotent

AbstractBiological tissues have complex, three-dimensional (3D) organizations of cells and matrix factors that provide the architecture necessary to meet morphogenic and functional demands. Disordered cell alignment is associated with congenital heart disease, cardiomyopathy, and neurodegenerative diseases and repairing or replacing these tissues using engineered constructs may improve regenerative capacity. However, optimizing cell alignment within engineered tissues requires quantitative 3D data on cell orientations and both efficient and validated processing algorithms. We developed an automated method to measure local 3D orientations based on structure tensor analysis and incorporated an adaptive subregion size to account for multiple scales. Our method calculates the statistical concentration parameter,κ, to quantify alignment, as well as the traditional orientational order parameter. We validated our method using synthetic images and accurately measured principal axis and concentration. We then applied our method to confocal stacks of cleared, whole-mount engineered cardiac tissues generated from human-induced pluripotent stem cells or embryonic chick cardiac cells and quantified cardiomyocyte alignment. We found significant differences in alignment based on cellular composition and tissue geometry. These results from our synthetic images and confocal data demonstrate the efficiency and accuracy of our method to measure alignment in 3D tissues.

scholarly journals Characterization of Mice Deficient in the Src Family Nonreceptor Tyrosine Kinase Frk/rak

2002 ◽  
Vol 22 (14) ◽  
pp. 5235-5247 ◽  
Author(s):  
Subhashini Chandrasekharan ◽  
Ting Hu Qiu ◽  
Nawal Alkharouf ◽  
Kelly Brantley ◽  
James B. Mitchell ◽  
...  
Keyword(s):  
Morphological Changes ◽  
Expression Patterns ◽  
Developmental Expression ◽  
Epithelial Tissue ◽  
Intestinal Damage ◽  
Specific Expression ◽  
Nonreceptor Tyrosine Kinase ◽  
Euthyroid Sick Syndrome ◽  
Epithelial Tissues

ABSTRACT Frk/rak belongs to a novel family of Src kinases with epithelial tissue-specific expression. Although developmental expression patterns and functional overexpression in vitro have associated these kinases with growth suppression and differentiation, their physiological functions remain largely unknown. We therefore generated mice carrying a null mutation in iyk, the mouse homolog of Frk/rak. We report here that frk/rak−/− mice are viable, show similar growth rates to wild-type animals, and are fertile. Furthermore, a 2-year study of health and survival did not identify differences in the incidence and spectrum of spontaneous tumors or provide evidence of hyperplasias in frk/rak−/− epithelial tissues. Histological analysis of organs failed to reveal any morphological changes in epithelial tissues that normally express high levels of Frk/rak. Ultrastructural analysis of intestinal enterocytes did not identify defects in brush border morphology or structural polarization, demonstrating that Frk/rak is dispensable for intestinal cytodifferentiation. Additionally, frk/rak-null mice do not display altered sensitivity to intestinal damage induced by ionizing radiation. cDNA microarray analysis revealed an increase in c-src expression and identified subtle changes in the expression of genes regulated by thyroid hormones. Significant decreases in the circulating levels of T3 but not T4 hormone are consistent with this observation and reminiscent of euthyroid sick syndrome, a stress-associated clinical condition.

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