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.

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.

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

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.

Study of the influence of the efficiency of application of asphalt concrete reinforced by basaltic fiber

2021 ◽  
Vol 2021 ◽  
pp. 117-128
Author(s):  
Artur Onyshchenko ◽  
◽  
Mykola Garkusha ◽  
Oleksandr Fedorenko ◽  
Yevgen Plazii ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Asphalt Concrete ◽  
Materials Science ◽  
Shape Change ◽  
Construction Materials ◽  
Basalt Fiber ◽  
Physical And Mechanical Properties ◽  
Operating Conditions ◽  
Concrete Mix ◽  
The Impact

Introduction. Increasing the load on highways and constantly increasing the intensity of traffic requires the use of road construction materials with improved physical and mechanical properties. Asphalt concrete is one of the most common and effective materials, which allows to provide the necessary strength and durability of the pavement structure. However, the use of traditional materials for its preparation - mineral material and road bitumen has a limited resource, which does not always meet traffic conditions. Modern scientific research in materials science allows to use mixtures of asphalt concrete and asphalt concrete road with the use of basalt fiber.Apply mixtures of asphalt concrete and asphalt concrete road with the use of basalt fiber, allows to increase the mechanical characteristics - tensile strength and resistance to fatigue from repeated loads, which increases the crack resistance of asphalt concrete layers of pavement structures, as well as increases resistance to shape change. accumulation of residual deformations.Problem Statement. From the literature analysis it is established that the coating of non-rigid pavement is in difficult operating conditions, which is confirmed by the intensive growth of defects in the form of tracks, landslides, inflows, cracks, due to increasing parameters of transport loads and high summer temperatures, so there is a need new materials.Purpose. Is to study the impact of the effectiveness of asphalt concrete reinforced with basalt fiber.Results. The results of physical and mechanical properties of asphalt concretes with the use of basalt fiber are obtained. The results of formation of residual deformations in the form of track in asphalt concrete with the use of basalt fiber are obtained. As a result of the conducted researches the analysis of efficiency of application of basalt fiber in asphalt concrete mix is executed.On the basis of the carried-out researches the basic requirements to asphalt concrete mix with use of basalt fiber are establishedConclusions. The research results were used in the development of regulations for the design, construction and repair of asphalt layers of roads in Ukraine.Keywords: asphalt concrete road with basalt fiber, asphalt concrete mixes with basalt fiber, loading, covering, stability, temperature.

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.

Implantation of Induced Pluripotent Stem Cell–Derived Tracheal Epithelial Cells

2017 ◽  
Vol 126 (7) ◽  
pp. 517-524 ◽  
Author(s):  
Masakazu Ikeda ◽  
Mitsuyoshi Imaizumi ◽  
Susumu Yoshie ◽  
Ryosuke Nakamura ◽  
Koshi Otsuki ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Induced Pluripotent Stem Cell ◽  
Embryoid Bodies ◽  
Epithelial Tissue ◽  
Tracheal Epithelial Cells ◽  
Epithelial Regeneration ◽  
Epithelial Tissues ◽  
Nude Rats ◽  
Tracheal Epithelial ◽  
Induced Pluripotent

Objectives: Compared with using autologous tissue, the use of artificial materials in the regeneration of tracheal defects is minimally invasive. However, this technique requires early epithelialization on the inner side of the artificial trachea. After differentiation from induced pluripotent stem cells (iPSCs), tracheal epithelial tissues may be used to produce artificial tracheas. Herein, we aimed to demonstrate that after differentiation from fluorescent protein-labeled iPSCs, tracheal epithelial tissues survived in nude rats with tracheal defects. Methods: Red fluorescent tdTomato protein was electroporated into mouse iPSCs to produce tdTomato-labeled iPSCs. Embryoid bodies derived from these iPSCs were then cultured in differentiation medium supplemented with growth factors, followed by culture on air-liquid interfaces for further differentiation into tracheal epithelium. The cells were implanted with artificial tracheas into nude rats with tracheal defects on day 26 of cultivation. On day 7 after implantation, the tracheas were exposed and examined histologically. Results: Tracheal epithelial tissue derived from tdTomato-labeled iPSCs survived in the tracheal defects. Moreover, immunochemical analyses showed that differentiated tissues had epithelial structures similar to those of proximal tracheal tissues. Conclusions: After differentiation from iPSCs, tracheal epithelial tissues survived in rat bodies, warranting the use of iPSCs for epithelial regeneration in tracheal defects.

scholarly journals Overlapping Roles of Drosophila Drak and Rok Kinases in Epithelial Tissue Morphogenesis

2010 ◽  
Vol 21 (16) ◽  
pp. 2869-2879 ◽  
Author(s):  
Dagmar Neubueser ◽  
David R. Hipfner
Keyword(s):  
Rho Gtpase ◽  
Actin Dynamics ◽  
Signaling Networks ◽  
Epithelial Tissue ◽  
Nonmuscle Myosin ◽  
Dynamic Regulation ◽  
Epithelial Tissues ◽  
Nonmuscle Myosin Ii ◽  
Death Associated Protein Kinase

Dynamic regulation of cytoskeletal contractility through phosphorylation of the nonmuscle Myosin-II regulatory light chain (MRLC) provides an essential source of tension for shaping epithelial tissues. Rho GTPase and its effector kinase ROCK have been implicated in regulating MRLC phosphorylation in vivo, but evidence suggests that other mechanisms must be involved. Here, we report the identification of a single Drosophila homologue of the Death-associated protein kinase (DAPK) family, called Drak, as a regulator of MRLC phosphorylation. Based on analysis of null mutants, we find that Drak broadly promotes proper morphogenesis of epithelial tissues during development. Drak activity is largely redundant with that of the Drosophila ROCK orthologue, Rok, such that it is essential only when Rok levels are reduced. We demonstrate that these two kinases synergistically promote phosphorylation of Spaghetti squash (Sqh), the Drosophila MRLC orthologue, in vivo. The lethality of drak/rok mutants can be rescued by restoring Sqh activity, indicating that Sqh is the critical common effector of these two kinases. These results provide the first evidence that DAPK family kinases regulate actin dynamics in vivo and identify Drak as a novel component of the signaling networks that shape epithelial tissues.

scholarly journals Taking the strain: quantifying the contributions of all cell behaviours to changes in epithelial shape

2017 ◽  
Vol 372 (1720) ◽  
pp. 20150513 ◽  
Author(s):  
Guy B. Blanchard
Keyword(s):  
Mechanical Properties ◽  
Cell Division ◽  
Cell Shape ◽  
Shape Change ◽  
Tissue Mechanics ◽  
Computer Assisted ◽  
Strain Rates ◽  
Cell Shape Change ◽  
Tissue Strain ◽  
Tissue Deformations

Computer-assisted tracking of the shapes of many cells over long periods of development has driven the exploration of novel ways to quantify the contributions of different cell behaviours to morphogenesis. A handful of similar methods have now been published that are used to calculate tissue deformations (strain rates) in epithelia. These methods are further used to quantify strain rates attributable to each of the cell behaviours in the tissue, such as cell shape change, cell rearrangement and cell division, that together sum to the tissue strain rates. In this review, aimed at developmental biologists, I will introduce the general approach, characterize differences in current approaches and highlight extensions of these methods that remain to be fully explored. The methods will make a major contribution to the emerging field of tissue mechanics. Precisely quantified strain rates are an essential first step towards exploring constitutive equations relating stress to strain via tissue mechanical properties. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’.

scholarly journals Non-autonomous induction of epithelial lineage infidelity and hyperplasia by DNA damage

2019 ◽  
Author(s):  
Lindsey Seldin ◽  
Ian G. Macara
Keyword(s):  
Dna Damage ◽  
Stem Cell ◽  
Mammary Gland ◽  
Hair Follicle ◽  
Epithelial Tissue ◽  
Cell Hyperplasia ◽  
Stromal Fibroblasts ◽  
Epithelial Tissues ◽  
Lineage Infidelity ◽  
Genotoxic Agents

ABSTRACTSeveral epithelial tissues contain stem cell reserves to replenish cells lost during normal homeostasis or upon injury. However, how epithelial tissues respond to distinct types of damage, and how stem cell plasticity and proliferation are regulated in these contexts, remain poorly understood. Here, we reveal that genotoxic agents, but not mechanical damage, induce hyperplasia and lineage infidelity in three related epithelial tissues: the mammary gland, interfollicular epidermis and hair follicle. Furthermore, DNA damage also promotes stromal proliferation. In the mammary gland, we find that DNA damage activates multipotency within the myoepithelial population and hyper-proliferation of their luminal progeny, resulting in tissue disorganization. Additionally, in epidermal and hair follicle epithelia, DNA damage induces basal cell hyperplasia with the formation of abnormal, multi-layered K14+/K10+ cells. This behavior does not involve apoptosis or immunity, and is epithelial cell non-autonomous; stromal fibroblasts are both necessary and sufficient to induce the epithelial response. Thus, genotoxic agents that are used chemotherapeutically to promote cancer cell death can have the opposite effect on wild-type epithelial tissue, paradoxically promoting hyperplasia and inducing both stemness and lineage infidelity.

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