scholarly journals A feedback mechanism converts individual cell features into a supracellular ECM structure in Drosophila trachea

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Arzu Öztürk-Çolak ◽  
Bernard Moussian ◽  
Sofia J Araújo ◽  
Jordi Casanova
Keyword(s):  
Extracellular Matrix ◽  
Individual Cell ◽  
Active Role ◽  
Feedback Mechanism ◽  
Cell Junctions ◽  
Complex Relationship ◽  
Tracheal System ◽  
Key Players ◽  
Active Feedback ◽  
Drosophila Trachea

The extracellular matrix (ECM), a structure contributed to and commonly shared by many cells in an organism, plays an active role during morphogenesis. Here, we used the Drosophila tracheal system to study the complex relationship between the ECM and epithelial cells during development. We show that there is an active feedback mechanism between the apical ECM (aECM) and the apical F-actin in tracheal cells. Furthermore, we reveal that cell-cell junctions are key players in this aECM patterning and organisation and that individual cells contribute autonomously to their aECM. Strikingly, changes in the aECM influence the levels of phosphorylated Src42A (pSrc) at cell junctions. Therefore, we propose that Src42A phosphorylation levels provide a link for the ECM environment to ensure proper cytoskeletal organisation.

scholarly journals Enhanced Piezoelectric Fibered Extracellular Matrix to Promote Cardiomyocyte Maturation and Tissue Formation: A 3D Computational Model

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 135
Author(s):  
Pau Urdeitx ◽  
Mohamed H. Doweidar
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Computational Models ◽  
Cell Junctions ◽  
Tissue Formation ◽  
Cardiac Muscle Cells ◽  
Cell Processes ◽  
Electrical Stimuli ◽  
Cell Cell

Mechanical and electrical stimuli play a key role in tissue formation, guiding cell processes such as cell migration, differentiation, maturation, and apoptosis. Monitoring and controlling these stimuli on in vitro experiments is not straightforward due to the coupling of these different stimuli. In addition, active and reciprocal cell–cell and cell–extracellular matrix interactions are essential to be considered during formation of complex tissue such as myocardial tissue. In this sense, computational models can offer new perspectives and key information on the cell microenvironment. Thus, we present a new computational 3D model, based on the Finite Element Method, where a complex extracellular matrix with piezoelectric properties interacts with cardiac muscle cells during the first steps of tissue formation. This model includes collective behavior and cell processes such as cell migration, maturation, differentiation, proliferation, and apoptosis. The model has employed to study the initial stages of in vitro cardiac aggregate formation, considering cell–cell junctions, under different extracellular matrix configurations. Three different cases have been purposed to evaluate cell behavior in fibered, mechanically stimulated fibered, and mechanically stimulated piezoelectric fibered extra-cellular matrix. In this last case, the cells are guided by the coupling of mechanical and electrical stimuli. Accordingly, the obtained results show the formation of more elongated groups and enhancement in cell proliferation.

scholarly journals Harnessing Extracellular Matrix Biology for Tumor Drug Delivery

2021 ◽  
Vol 11 (2) ◽  
pp. 88
Author(s):  
Nithya Subrahmanyam ◽  
Hamidreza Ghandehari
Keyword(s):  
Drug Delivery ◽  
Extracellular Matrix ◽  
Cancer Progression ◽  
Active Role ◽  
Reciprocal Relationship ◽  
Design Parameters ◽  
Cancer Etiology ◽  
Cell Life ◽  
Tumor Drug Delivery ◽  
Signaling Interactions

The extracellular matrix (ECM) plays an active role in cell life through a tightly controlled reciprocal relationship maintained by several fibrous proteins, enzymes, receptors, and other components. It is also highly involved in cancer progression. Because of its role in cancer etiology, the ECM holds opportunities for cancer therapy on several fronts. There are targets in the tumor-associated ECM at the level of signaling molecules, enzyme expression, protein structure, receptor interactions, and others. In particular, the ECM is implicated in invasiveness of tumors through its signaling interactions with cells. By capitalizing on the biology of the tumor microenvironment and the opportunities it presents for intervention, the ECM has been investigated as a therapeutic target, to facilitate drug delivery, and as a prognostic or diagnostic marker for tumor progression and therapeutic intervention. This review summarizes the tumor ECM biology as it relates to drug delivery with emphasis on design parameters targeting the ECM.

scholarly journals Cellular dynamics of EMT: lessons from live in vivo imaging of embryonic development

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jeffrey D. Amack
Keyword(s):  
Extracellular Matrix ◽  
Embryonic Development ◽  
In Vivo Imaging ◽  
Cytoskeletal Proteins ◽  
Cell Junctions ◽  
Model Organisms ◽  
Cellular Dynamics ◽  
Mesenchymal Transition ◽  
Cell Cell

AbstractEpithelial-mesenchymal transition (EMT) refers to a process in which epithelial cells lose apical-basal polarity and loosen cell–cell junctions to take on mesenchymal cell morphologies and invasive properties that facilitate migration through extracellular matrix. EMT—and the reverse mesenchymal-epithelial transition (MET)—are evolutionarily conserved processes that are used throughout embryonic development to drive tissue morphogenesis. During adult life, EMT is activated to close wounds after injury, but also can be used by cancers to promote metastasis. EMT is controlled by several mechanisms that depend on context. In response to cell–cell signaling and/or interactions with the local environment, cells undergoing EMT make rapid changes in kinase and adaptor proteins, adhesion and extracellular matrix molecules, and gene expression. Many of these changes modulate localization, activity, or expression of cytoskeletal proteins that mediate cell shape changes and cell motility. Since cellular changes during EMT are highly dynamic and context-dependent, it is ideal to analyze this process in situ in living organisms. Embryonic development of model organisms is amenable to live time-lapse microscopy, which provides an opportunity to watch EMT as it happens. Here, with a focus on functions of the actin cytoskeleton, I review recent examples of how live in vivo imaging of embryonic development has led to new insights into mechanisms of EMT. At the same time, I highlight specific developmental processes in model embryos—gastrulation in fly and mouse embryos, and neural crest cell development in zebrafish and frog embryos—that provide in vivo platforms for visualizing cellular dynamics during EMT. In addition, I introduce Kupffer’s vesicle in the zebrafish embryo as a new model system to investigate EMT and MET. I discuss how these systems have provided insights into the dynamics of adherens junction remodeling, planar cell polarity signaling, cadherin functions, and cytoskeletal organization during EMT, which are not only important for understanding development, but also cancer progression. These findings shed light on mechanisms of actin cytoskeletal dynamics during EMT, and feature live in vivo imaging strategies that can be exploited in future work to identify new mechanisms of EMT and MET.

scholarly journals Scar Formation: Cellular Mechanisms

2020 ◽  
pp. 19-26
Author(s):  
Ian A. Darby ◽  
Alexis Desmoulière
Keyword(s):  
Extracellular Matrix ◽  
Tissue Repair ◽  
New Drugs ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Hypertrophic Scars ◽  
Cellular Mechanisms ◽  
Skin Repair ◽  
Cell Quiescence ◽  
Key Players

AbstractFibroblasts are key players in the maintenance of skin homeostasis and in orchestrating physiological tissue repair. Fibroblasts secrete and are embedded in a sophisticated extracellular matrix, and a complex and interactive dialogue exists between fibroblasts and their microenvironment. In addition to the secretion of the extracellular matrix, fibroblasts and myofibroblasts secrete extracellular matrix remodeling enzymes, matrix metalloproteinases and their inhibitors, and tissue inhibitors of metalloproteinases and are thus able to remodel the extracellular matrix. Myofibroblasts and their microenvironment form a network that evolves during tissue repair. This network has reciprocal actions affecting cell differentiation, cell proliferation, cell quiescence, or apoptosis and has actions on growth factor bioavailability by binding, sequestration, and activation. Mechanical forces also play a role in regulating the myofibroblast phenotype as cells are subjected to mechanical stress and mechanical signaling is activated. Innervation is also involved in both skin repair processes and differentiation of myofibroblasts. In pathological situations, for example, in excessive scarring, the dialogue between myofibroblasts and their microenvironment can be altered or disrupted, leading to defects in tissue repair or to pathological scarring, such as that seen in hypertrophic scars. Better understanding of the intimate dialogue between myofibroblasts and their local microenvironment is needed and will be important in aiding the identification of new therapeutic targets and discovery of new drugs to treat or prevent aberrant tissue repair and scarring.

scholarly journals The Extracellular Matrix and Pancreatic Cancer: A Complex Relationship

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 316 ◽  
Author(s):  
Maximilian Weniger ◽  
Kim Honselmann ◽  
Andrew Liss
Keyword(s):  
Extracellular Matrix ◽  
Therapeutic Strategies ◽  
Ductal Adenocarcinoma ◽  
Interstitial Tissue ◽  
Complex Relationship ◽  
Tumor Perfusion ◽  
Tissue Pressure ◽  
Physical Cues ◽  
Proliferation And Metastasis ◽  
Mechanical Influence

Pancreatic ductal adenocarcinoma (PDAC) has an extraordinarily dense fibrotic stroma that impedes tumor perfusion and delivery of anticancer drugs. Since the extracellular matrix (ECM) comprises the bulk of the stroma, it is primarily responsible for the increased interstitial tissue pressure and stiff mechanical properties of the stroma. Besides its mechanical influence, the ECM provides important biochemical and physical cues that promote survival, proliferation, and metastasis. By serving as a nutritional source, the ECM also enables PDAC cells to survive under the nutrient-poor conditions. While therapeutic strategies using stroma-depleting drugs have yielded disappointing results, an increasing body of research indicates the ECM may offer a variety of potential therapeutic targets. As preclinical studies of ECM-targeted drugs have shown promising effects, a number of clinical trials are currently investigating agents with the potential to advance the future treatment of PDAC. Thus, the present review seeks to give an overview of the complex relationship between the ECM and PDAC.

Fine structure of the regressing interdigital membranes during the formation of the digits of the chick embryo leg bud

Development ◽  
1983 ◽  
Vol 78 (1) ◽  
pp. 195-209
Author(s):  
J. M. Hurle ◽  
M. A. Fernandez-Teran
Keyword(s):  
Extracellular Matrix ◽  
Fine Structure ◽  
Chick Embryo ◽  
Basal Lamina ◽  
Ultrastructural Study ◽  
Active Role ◽  
Epithelial Tissue ◽  
Complex Process ◽  
Cell Processes ◽  
Collagenous Material

There is recent evidence showing that in addition to the well-known mesenchymal necrotic mechanism involved in the disappearance of the interdigital membranes, the ectodermal tissue may also play an active role in the formation of the free digits of most vertebrates. Ultrastructural study of the regressing interdigital membrane of the chick leg revealed significant changes at the epitheliomesenchymal interface. Disruptions of the ectodermal basal lamina and an intense deposition of collagenous material were the most conspicuous changes observed in the extracellular matrix. In addition the basal ectodermal cells showed prominent cell processes projected into the mesenchymal core of the membrane, and mesenchymal macrophages appeared to migrate through the epithelial tissue to be detached into the amniotic sac. It is concluded from our results that the elimination of the interdigital membranes is a complex process requiring the interaction of all the tissue components of the membrane.

scholarly journals Sensory reweighting dynamics in human postural control

2014 ◽  
Vol 111 (9) ◽  
pp. 1852-1864 ◽  
Author(s):  
Lorenz Assländer ◽  
Robert J. Peterka
Keyword(s):  
Balance Control ◽  
High Amplitude ◽  
Feedback Mechanism ◽  
Sensory Reweighting ◽  
Healthy Humans ◽  
Active Feedback ◽  
Orientation Cues ◽  
Young Subjects ◽  
Low Amplitude ◽  
Control Balance

Healthy humans control balance during stance by using an active feedback mechanism that generates corrective torque based on a combination of movement and orientation cues from visual, vestibular, and proprioceptive systems. Previous studies found that the contribution of each of these sensory systems changes depending on perturbations applied during stance and on environmental conditions. The process of adjusting the sensory contributions to balance control is referred to as sensory reweighting. To investigate the dynamics of reweighting for the sensory modalities of vision and proprioception, 14 healthy young subjects were exposed to six different combinations of continuous visual scene and platform tilt stimuli while sway responses were recorded. Stimuli consisted of two components: 1) a pseudorandom component whose amplitude periodically switched between low and high amplitudes and 2) a low-amplitude sinusoidal component whose amplitude remained constant throughout a trial. These two stimuli were mathematically independent of one another and, thus, permitted separate analyses of sway responses to the two components. For all six stimulus combinations, the sway responses to the constant-amplitude sine were influenced by the changing amplitude of the pseudorandom component in a manner consistent with sensory reweighting. Results show clear evidence of intra- and intermodality reweighting. Reweighting dynamics were asymmetric, with slower reweighting dynamics following a high-to-low transition in the pseudorandom stimulus amplitude compared with low-to-high amplitude shifts, and were also slower for inter- compared with intramodality reweighting.

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