scholarly journals Integrating planar polarity and tissue mechanics in computational models of epithelial morphogenesis

2017 ◽  
Author(s):  
Katherine H. Fisher ◽  
David Strutt ◽  
Alexander G. Fletcher
Keyword(s):  
Cell Mechanics ◽  
Computational Models ◽  
Imaging Techniques ◽  
Cell Signalling ◽  
Tissue Mechanics ◽  
Neural Tube Closure ◽  
Epithelial Morphogenesis ◽  
Planar Polarity ◽  
Animal Tissues ◽  
Developmental Defects

AbstractCells in many epithelial tissues are polarised orthogonally to their apicobasal axis. Such planar polarity ensures that tissue shape and structure are properly organised. Disruption of planar polarity can result in developmental defects such as failed neural tube closure and cleft palette. Recent advances in molecular and live-imaging techniques have implicated both secreted morphogens and mechanical forces as orienting cues for planar polarisation. Components of planar polarity pathways act upstream of cytoskeletal effectors, which can alter cell mechanics in a polarised manner. The study of cell polarisation thus provides a system for dissecting the interplay between chemical and mechanical signals in development. Here, we discuss how different computational models have contributed to our understanding of the mechanisms underlying planar polarity in animal tissues, focusing on recent efforts to integrate cell signalling and tissue mechanics. We conclude by discussing ways in which computational models could be improved to further our understanding of how planar polarity and tissue mechanics are coordinated during development.

Development of a Discrete Finite Element Cell Model

2007 ◽  
Author(s):  
Karen M. Coghlan ◽  
Patrick McGarry ◽  
Mohammad R. K. Mofrad ◽  
Peter E. McHugh
Keyword(s):  
Finite Element ◽  
Structural Properties ◽  
Continuum Mechanics ◽  
Cell Mechanics ◽  
Computational Models ◽  
Cell Model ◽  
Alternative Approach ◽  
Discrete Nature ◽  
Discrete Finite Element

Computational models have proven useful in the study of cell mechanics and mechanotransduction. While most finite element (FE) models of cells are commonly described in terms of the laws of continuum mechanics, a model that can accurately represent the microstructure of the filamentous network of the cytoskeleton would be required to relate mechanics to biology at the microscale level. An alternative approach to a continuum is presented here, whereby the discrete nature of the cytoskeleton of the cell is emphasized and the known structural properties of the cytoskeleton of the cell are utilized.

Nanodomains in biological membranes

2015 ◽  
Vol 57 ◽  
pp. 93-107 ◽  
Author(s):  
Yuanqing Ma ◽  
Elizabeth Hinde ◽  
Katharina Gaus
Keyword(s):  
Lipid Rafts ◽  
T Cell Activation ◽  
Protein Interactions ◽  
Lipid Raft ◽  
Cell Activation ◽  
Imaging Techniques ◽  
Cell Signalling ◽  
Recent Developments ◽  
Lipid Protein Interactions ◽  
High Dynamics

Lipid rafts are defined as cholesterol- and sphingomyelin-enriched membrane domains in the plasma membrane of cells that are highly dynamic and cannot be resolved with conventional light microscopy. Membrane proteins that are embedded in the phospholipid matrix can be grouped into raft and non-raft proteins based on their association with detergent-resistant membranes in biochemical assays. Selective lipid–protein interactions not only produce heterogeneity in the membrane, but also cause the spatial compartmentalization of membrane reactions. It has been proposed that lipid rafts function as platforms during cell signalling transduction processes such as T-cell activation (see Chapter 13 (pages 165–175)). It has been proposed that raft association co-localizes specific signalling proteins that may yield the formation of the observed signalling microclusters at the immunological synapses. However, because of the nanometre size and high dynamics of lipid rafts, direct observations have been technically challenging, leading to an ongoing discussion of the lipid raft model and its alternatives. Recent developments in fluorescence imaging techniques have provided new opportunities to investigate the organization of cell membranes with unprecedented spatial resolution. In this chapter, we describe the concept of the lipid raft and alternative models and how new imaging technologies have advanced these concepts.

scholarly journals Study of Biaxial Mechanical Properties of the Passive Pig Heart: Material Characterisation and Categorisation of Regional Differences

2020 ◽  
Author(s):  
Fulufhelo Nemavhola
Keyword(s):  
Mechanical Properties ◽  
Computational Models ◽  
Heart Diseases ◽  
Interventricular Septum ◽  
Constitutive Modelling ◽  
Tissue Mechanics ◽  
Material Behaviour ◽  
Biaxial Testing ◽  
African Countries ◽  
Biaxial Tests

Regional mechanics of the heart is vital in the development of accurate computational models for the pursuit of relevant therapies. Challenges related to heart dysfunctioning are the most important sources of mortality in the world. For example, myocardial infarction (MI) is the foremost killer in sub-Saharan African countries. Mechanical characterisation plays an important role in achieving accurate material behaviour. Material behaviour and constitutive modelling are essential for accurate development of computational models. In most cases previously, the mechanical properties of the heart myocardium were assumed to be homogeneous. The main objective of this paper is to determine the mechanical material properties of healthy porcine myocardium in three regions, namely left ventricle (LV), mid-wall/interventricular septum (MDW) and right ventricle (RV). The biomechanical properties of the pig heart RV, LV and MDW were characterised using biaxial testing. The biaxial tests show the pig heart myocardium behaves non-linearly, heterogeneously and anisotropically. In this study, it was shown that RV, LV and MDW may exhibit slightly different mechanical properties. Data presented here may be helpful in regional tissue mechanics, especially for the understanding of various heart diseases and development of new therapies.

scholarly journals Passive Biaxial Tensile Dataset of Three Main Rat Heart Myocardia: Left Ventricle, Mid-Wall and Right Ventricle

2021 ◽  
Author(s):  
Fulufhelo Nemavhola ◽  
Harry Ngwangwa ◽  
Neil Davies ◽  
Thoams Franz
Keyword(s):  
Left Ventricle ◽  
Right Ventricle ◽  
Rat Heart ◽  
Computational Models ◽  
Heart Diseases ◽  
Tissue Mechanics ◽  
Soft Tissue Mechanics ◽  
Biaxial Tensile ◽  
As Stress

This article presents raw data of biaxial tensile measurements of rat heart passive myocardium conducted in lab scale environment. The passive myocardium of the rat was divided into three regions, namely: left ventricle, mid-wall and right ventricle. The biaxial dataset of passive rat myocardia is presented as stress vs strain of the passive rat myocardium in various regions. The determination of valid material properties of the heart plays an important role in the development computational models. These computational models are useful in studying various scenarios and mechanisms of heart diseases. In addition, valid and accurate materials are critical in the development of new therapies. The dataset presented here is useful in the area of soft tissue mechanics including studying the mechanisms of heart diseases such as myocardial infarction. Accordingly, the evaluation of stress and strain in left ventricle, mid-wall and right ventricle was performed.

Cardiac Assist With a Twist: Apical Torsion as a Means to Improve Failing Heart Function

2011 ◽  
Vol 133 (10) ◽  
Author(s):  
Dennnis R. Trumble ◽  
Walter E. McGregor ◽  
Roy C. P. Kerckhoffs ◽  
Lewis K. Waldman
Keyword(s):  
Stroke Volume ◽  
Computer Model ◽  
Computational Models ◽  
Heart Function ◽  
Imaging Techniques ◽  
Wall Stress ◽  
Similar Proportion ◽  
Stroke Work ◽  
Drug Induced

Changes in muscle fiber orientation across the wall of the left ventricle (LV) cause the apex of the heart to turn 10–15 deg in opposition to its base during systole and are believed to increase stroke volume and lower wall stress in healthy hearts. Studies show that cardiac torsion is sensitive to various disease states, which suggests that it may be an important aspect of cardiac function. Modern imaging techniques have sparked renewed interest in cardiac torsion dynamics, but no work has been done to determine whether mechanically augmented apical torsion can be used to restore function to failing hearts. In this report, we discuss the potential advantages of this approach and present evidence that turning the cardiac apex by mechanical means can displace a clinically significant volume of blood from failing hearts. Computational models of normal and reduced-function LVs were created to predict the effects of applied apical torsion on ventricular stroke work and wall stress. These same conditions were reproduced in anesthetized pigs with drug-induced heart failure using a custom apical torsion device programmed to rotate over various angles during cardiac systole. Simulations of applied 90 deg torsion in a prolate spheroidal computational model of a reduced-function pig heart produced significant increases in stroke work (25%) and stroke volume with reduced fiber stress in the epicardial region. These calculations were in substantial agreement with corresponding in vivo measurements. Specifically, the computer model predicted torsion-induced stroke volume increases from 13.1 to 14.4 mL (9.9%) while actual stroke volume in a pig heart of similar size and degree of dysfunction increased from 11.1 to 13.0 mL (17.1%). Likewise, peak LV pressures in the computer model rose from 85 to 95 mm Hg (11.7%) with torsion while maximum ventricular pressures in vivo increased in similar proportion, from 55 to 61 mm Hg (10.9%). These data suggest that: (a) the computer model of apical torsion developed for this work is a fair and accurate predictor of experimental outcomes, and (b) supra-physiologic apical torsion may be a viable means to boost cardiac output while avoiding blood contact that occurs with other assist methods.

scholarly journals Developmental plasticity, cell fate specification and morphogenesis in the early mouse embryo

2014 ◽  
Vol 369 (1657) ◽  
pp. 20130538 ◽  
Author(s):  
Ivan Bedzhov ◽  
Sarah J. L. Graham ◽  
Chuen Yan Leung ◽  
Magdalena Zernicka-Goetz
Keyword(s):  
Cell Fate ◽  
Mouse Embryo ◽  
Developmental Plasticity ◽  
Molecular Mechanisms ◽  
Imaging Techniques ◽  
Cell Signalling ◽  
Three Dimensional ◽  
Early Embryo ◽  
Mammalian Development ◽  
Cell Fate Decisions

A critical point in mammalian development is when the early embryo implants into its mother's uterus. This event has historically been difficult to study due to the fact that it occurs within the maternal tissue and therefore is hidden from view. In this review, we discuss how the mouse embryo is prepared for implantation and the molecular mechanisms involved in directing and coordinating this crucial event. Prior to implantation, the cells of the embryo are specified as precursors of future embryonic and extra-embryonic lineages. These preimplantation cell fate decisions rely on a combination of factors including cell polarity, position and cell–cell signalling and are influenced by the heterogeneity between early embryo cells. At the point of implantation, signalling events between the embryo and mother, and between the embryonic and extraembryonic compartments of the embryo itself, orchestrate a total reorganization of the embryo, coupled with a burst of cell proliferation. New developments in embryo culture and imaging techniques have recently revealed the growth and morphogenesis of the embryo at the time of implantation, leading to a new model for the blastocyst to egg cylinder transition. In this model, pluripotent cells that will give rise to the fetus self-organize into a polarized three-dimensional rosette-like structure that initiates egg cylinder formation.

scholarly journals Tissue Fluidity Promotes Epithelial Wound Healing

2018 ◽  
Author(s):  
Robert J. Tetley ◽  
Michael F. Staddon ◽  
Shiladitya Banerjee ◽  
Yanlan Mao
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Tissue Mechanics ◽  
Animal Tissues ◽  
Wound Edge ◽  
Surrounding Environment ◽  
Epithelial Wound Healing ◽  
Repair Mechanisms ◽  
Tissue Tension

SummaryEpithelial tissues are inevitably damaged from time to time and must therefore have robust repair mechanisms. The behaviour of tissues depends on their mechanical properties and those of the surrounding environment1. However, it remains poorly understood how tissue mechanics regulates wound healing, particularly in in vivo animal tissues. Here we show that by tuning epithelial cell junctional tension, we can alter the rate of wound healing. We observe cells moving past each other at the wound edge by intercalating, like molecules in a fluid, resulting in seamless wound closure. Using a computational model, we counterintuitively predict that an increase in tissue fluidity, via a reduction in junctional tension, can accelerate the rate of wound healing. This is contrary to previous evidence that actomyosin tensile structures are important for wound closure2–6. When we experimentally reduce tissue tension, cells intercalate faster and wounds close in less time. The role we describe for tissue fluidity in wound healing, in addition to its known roles in developing7,8 and mature tissues9, reinforces the importance of the fluid state of a tissue.

scholarly journals Information Flow in Planar Polarity

2017 ◽  
Author(s):  
Katherine H Fisher ◽  
David Strutt ◽  
Alexander G Fletcher
Keyword(s):  
Information Flow ◽  
Double Mutant ◽  
Protein Complexes ◽  
Individual Cell ◽  
Cell Signalling ◽  
Computational Modelling ◽  
Planar Polarity ◽  
Signalling Models ◽  
Scale Properties ◽  
Insight Into

SummaryIn developing tissues, sheets of cells become planar polarised, enabling coordination of cell behaviours. It has been suggested that ‘signalling’ of polarity information between cells may occur either bidirectionally or monodirectionally between the molecules Frizzled (Fz) and Van Gogh (Vang). Using computational modelling we find that both bidirectional and monodirectional signalling models reproduce known non-autonomous phenotypes derived from patches of mutant tissue of key molecules, but predict different phenotypes from double mutant tissue, which have previously given conflicting experimental results. Consequently, we re-examine experimental phenotypes in the Drosophila wing, concluding that signalling is most likely bidirectional. Our modelling suggests that bidirectional signalling can be mediated either indirectly via bidirectional feedbacks between asymmetric intercellular protein complexes, or directly via different affinities for protein binding in intercellular complexes, suggesting future avenues for investigation. Our findings offer insight into mechanisms of juxtacrine cell signalling and how tissue-scale properties emerge from individual cell behaviours.

scholarly journals Association of aerobic glycolysis with the structural connectome reveals a benefit–risk balancing mechanism in the human brain

2020 ◽  
Vol 118 (1) ◽  
pp. e2013232118
Author(s):  
Yuhan Chen ◽  
Qixiang Lin ◽  
Xuhong Liao ◽  
Changsong Zhou ◽  
Yong He
Keyword(s):  
Human Brain ◽  
Computational Models ◽  
Aerobic Glycolysis ◽  
Imaging Techniques ◽  
Amyloid Β ◽  
Generation Task ◽  
Axonal Projection ◽  
Projection Length ◽  
The Relationship ◽  
Wiring Optimization

Aerobic glycolysis (AG), that is, the nonoxidative metabolism of glucose, contributes significantly to anabolic pathways, rapid energy generation, task-induced activity, and neuroprotection; yet high AG is also associated with pathological hallmarks such as amyloid-β deposition. An important yet unresolved question is whether and how the metabolic benefits and risks of brain AG is structurally shaped by connectome wiring. Using positron emission tomography and magnetic resonance imaging techniques as well as computational models, we investigate the relationship between brain AG and the macroscopic connectome. Specifically, we propose a weighted regional distance-dependent model to estimate the total axonal projection length of a brain node. This model has been validated in a macaque connectome derived from tract-tracing data and shows a high correspondence between experimental and estimated axonal lengths. When applying this model to the human connectome, we find significant associations between the estimated total axonal projection length and AG across brain nodes, with higher levels primarily located in the default-mode and prefrontal regions. Moreover, brain AG significantly mediates the relationship between the structural and functional connectomes. Using a wiring optimization model, we find that the estimated total axonal projection length in these high-AG regions exhibits a high extent of wiring optimization. If these high-AG regions are randomly rewired, their total axonal length and vulnerability risk would substantially increase. Together, our results suggest that high-AG regions have expensive but still optimized wiring cost to fulfill metabolic requirements and simultaneously reduce vulnerability risk, thus revealing a benefit–risk balancing mechanism in the human brain.

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