scholarly journals The Biomechanical Basis of Biased Epithelial Tube Elongation

2020 ◽  
Author(s):  
Steve Runser ◽  
Lisa Conrad ◽  
Harold Gómez ◽  
Christine Lang ◽  
Mathilde Dumond ◽  
...  

ABSTRACTDuring lung development, epithelial branches expand preferentially in longitudinal direction. This bias in outgrowth has been linked to a bias in cell shape and in the cell division plane. How such bias arises is unknown. Here, we show that biased epithelial outgrowth occurs independent of the surrounding mesenchyme. Biased outgrowth is also not the consequence of a growth factor gradient, as biased outgrowth is obtained with uniform growth factor cultures, and in the presence of the FGFR inhibitor SU5402. Furthermore, we note that epithelial tubes are largely closed during early lung and kidney development. By simulating the reported fluid flow inside segmented narrow epithelial tubes, we show that the shear stress levels on the apical surface are sufficient to explain the reported bias in cell shape and outgrowth. We use a cell-based vertex model to confirm that apical shear forces, unlike constricting forces, can give rise to both the observed bias in cell shapes and tube elongation. We conclude that shear stress may be a more general driver of biased tube elongation beyond its established role in angiogenesis.

2018 ◽  
Author(s):  
Ramya Balaji ◽  
Vanessa Weichselberger ◽  
Anne-Kathrin Classen

AbstractThe role of actomyosin contractility at epithelial adherens junctions has been extensively studied. However, little is known about how external forces are integrated to establish epithelial cell and organ shape in vivo. We use the Drosophila follicle epithelium to investigate how tension at adherens junctions is regulated to integrate external forces arising from changes in germline size and shape. We find that overall tension in the epithelium decreases despite pronounced growth of enclosed germline cells, suggesting that the epithelium relaxes to accommodate growth. However, we find local differences in adherens junction tension correlate with apposition to germline nurse cells or the oocyte. We demonstrate that medial Myosin II coupled to corrugating adherens junctions resists nurse cell-derived forces and thus maintains apical surface areas and cuboidal cell shapes. Furthermore, medial reinforcement of the apical surface ensures cuboidal-to-columnar cell shape transitions and imposes circumferential constraints on nurse cells guiding organ elongation. Our study provides insight into how tension within an adherens junction network integrates growth of a neighbouring tissue, mediates cell shape transitions and channels growth into organ elongation.


2019 ◽  
Author(s):  
Anna Stopka ◽  
Marco Kokic ◽  
Dagmar Iber

AbstractDuring morphogenesis, epithelial tubes elongate. In case of the mammalian lung, biased elongation has been linked to a bias in cell shape and cell division, but it has remained unclear whether a bias in cell shape along the axis of outgrowth is sufficient for biased outgrowth and how it arises. Here, we use our 2D cell-based tissue simulation software LBIBCell to investigate the conditions for biased epithelial outgrowth. We show that the observed bias in cell shape and cell division can result in the observed bias in outgrowth only in case of strong cortical tension, and comparison to biological data suggests that the cortical tension in epithelia is likely sufficient. We explore mechanisms that may result in the observed bias in cell division and cell shapes. To this end, we test the possibility that the surrounding tissue or extracellular matrix acts as a mechanical constraint that biases growth in longitudinal direction. While external compressive forces can result in the observed bias in outgrowth, we find that they do not result in the observed bias in cell shapes. We conclude that other mechanisms must exist that generate the bias in lung epithelial outgrowth.


2020 ◽  
Author(s):  
Amarendra Badugu ◽  
Andres Käch

AbstractHow cell shape and mechanics are organized in three dimensions during tissue morphogenesis is poorly understood. In the Drosophila wing imaginal disc, we examined the mechanical processes that determine the shape of epithelial cells. Since it has been known that basement membrane influences the mechanics intracellularly, we reexamined the material properties of the basement membrane with fluorescence and transmission electron microscopy in its native environment. Further, we investigated the effect on cell shape and tissue mechanics when disruptions were instigated at three different time scales: (1) short (seconds with laser cutting), (2) medium (minutes with drug treatments), and (3) long (days with RNAi interference). We found regions in which the basement membrane is much thicker and heterogeneous than previously reported. Disrupting the actin cytoskeleton through drug treatment affects cell shape only at the apical surface, while the shapes in the medial and basal surfaces were not altered. In contrast, when integrin function was inhibited via RNAi or basement membrane integrity was disrupted by drug treatment, the medial and basal cell shapes were affected. We propose that basement membrane thickness patterns determine the height and basal surface area of cells and the curvature of folds in the wing disc. Based on these findings and previous studies, we propose a model of how cell shapes and tissue properties were determined by highly local, modular apical and basal mechanics.Graphical abstract


2017 ◽  
Author(s):  
Ross Carter ◽  
Yara E. Sánchez-Corrales ◽  
Verônica A. Grieneisen ◽  
Athanasius F. M. Marée

AbstractD’Arcy Thompson emphasised the importance of surface tension as a potential driving force in establishing cell shape and topology within tissues. Leaf epidermal pavement cells grow into jigsaw-piece shapes, highly deviating from such classical forms. We investigate the topology of developing Arabidopsis leaves composed solely of pavement cells. Image analysis of around 50,000 cells reveals a clear and unique topological signature, deviating from previously studied epidermal tissues. This topological distribution is however established early during leaf development, already before the typical pavement cell shapes emerge, with topological homestasis maintained throughout growth and unaltered between division and maturation zones. Simulating graph models, we identify a heuristic cellular division rule that reproduces the observed topology. Our parsimonious model predicts how and when cells effectively place their division plane with respect to their neighbours. We verify the predicted dynamics through in vivo tracking of 800 mitotic events, and conclude that the distinct topology is not a direct consequence of the jigsaw-like shape of the cells, but rather owes itself to a strongly life-history-driven process, with limited impact from cell surface mechanics.Summary statementDevelopment of the Arabidopsis leaf epidermis topology is driven by deceptively simple rules of cell division, independent of surface tension, cell size and, often complex, cell shape.


2021 ◽  
Vol 22 (11) ◽  
pp. 5635
Author(s):  
Katharina Urschel ◽  
Miyuki Tauchi ◽  
Stephan Achenbach ◽  
Barbara Dietel

In the 1900s, researchers established animal models experimentally to induce atherosclerosis by feeding them with a cholesterol-rich diet. It is now accepted that high circulating cholesterol is one of the main causes of atherosclerosis; however, plaque localization cannot be explained solely by hyperlipidemia. A tremendous amount of studies has demonstrated that hemodynamic forces modify endothelial athero-susceptibility phenotypes. Endothelial cells possess mechanosensors on the apical surface to detect a blood stream-induced force on the vessel wall, known as “wall shear stress (WSS)”, and induce cellular and molecular responses. Investigations to elucidate the mechanisms of this process are on-going: on the one hand, hemodynamics in complex vessel systems have been described in detail, owing to the recent progress in imaging and computational techniques. On the other hand, investigations using unique in vitro chamber systems with various flow applications have enhanced the understanding of WSS-induced changes in endothelial cell function and the involvement of the glycocalyx, the apical surface layer of endothelial cells, in this process. In the clinical setting, attempts have been made to measure WSS and/or glycocalyx degradation non-invasively, for the purpose of their diagnostic utilization. An increasing body of evidence shows that WSS, as well as serum glycocalyx components, can serve as a predicting factor for atherosclerosis development and, most importantly, for the rupture of plaques in patients with high risk of coronary heart disease.


Nature ◽  
1972 ◽  
Vol 235 (5338) ◽  
pp. 366-366
Keyword(s):  

2005 ◽  
Vol 289 (2) ◽  
pp. H845-H851 ◽  
Author(s):  
Akhilesh K. Sista ◽  
Mary K. O'Connell ◽  
Tomoya Hinohara ◽  
Santosh S. Oommen ◽  
Brett E. Fenster ◽  
...  

Accumulating clinical evidence indicates increased aortic stiffness, an independent risk factor for cardiovascular and all-cause mortality, in type 2 diabetic and glucose-intolerant individuals. The present study sought to determine whether increased mechanical stiffness, an altered extracellular matrix, and a profibrotic gene expression profile could be observed in the aorta of the insulin-resistant Zucker fa/fa rat. Mechanical testing of Zucker fa/fa aortas showed increased vascular stiffness in longitudinal and circumferential directions compared with Zucker lean controls. Unequal elevations in developed strain favoring the longitudinal direction resulted in a loss of anisotropy. Real-time quantitative PCR and immunohistochemistry revealed increased expression of fibronectin and collagen IVα3 in the Zucker fa/fa aorta. In addition, expression of transforming growth factor-β and several Smad proteins was increased in vessels from insulin-resistant animals. In rat vascular smooth muscle cells, 12–18 h of exposure to insulin (100 nmol/l) enhanced transforming growth factor-β1 mRNA expression, implicating a role for hyperinsulinemia in vascular stiffness. Thus there is mechanical, structural, and molecular evidence of arteriosclerosis in the Zucker fa/fa rat at the glucose-intolerant, hyperinsulinemic stage.


2021 ◽  
Author(s):  
Shigehiro Hashimoto ◽  
Hiroki Yonezawa

Abstract A cell deforms and migrates on the scaffold under mechanical stimuli in vivo. In this study, a cell with division during shear stress stimulation has been observed in vitro. Before and after division, both migration and deformation of each cell were analyzed. To make a Couette-type shear flow, the medium was sandwiched between parallel disks (the lower stationary culture-disc and the upper rotating disk) with a constant gap. The wall shear stress (1.5 Pa < τ < 2 Pa) on the surface of the lower culture plate was controlled by the rotational speed of the upper disc. Myoblasts (C2C12: mouse myoblast cell line) were used in the test. After cultivation without flow for 24 hours for adhesion of the cells to the lower disk, constant τ was applied to the cells in the incubator for 7 days. The behavior of each cell during shear was tracked by time-lapse images observed by an inverted phase contrast microscope placed in the incubator. Experimental results show that each cell tends to divide after higher activities: deformation and migration. The tendency is remarkable at the shear stress of 1.5 Pa.


2000 ◽  
Vol 88 (3) ◽  
pp. 1127-1132 ◽  
Author(s):  
Brenda Russell ◽  
Delara Motlagh ◽  
William W. Ashley

What determines the shape, size, and force output of cardiac and skeletal muscle? Chicago architect Louis Sullivan (1856–1924), father of the skyscraper, observed that “form follows function.” This is as true for the structural elements of a striated muscle cell as it is for the architectural features of a building. Function is a critical evolutionary determinant, not form. To survive, the animal has evolved muscles with the capacity for dynamic responses to altered functional demand. For example, work against an increased load leads to increased mass and cross-sectional area (hypertrophy), which is directly proportional to an increased potential for force production. Thus a cell has the capacity to alter its shape as well as its volume in response to a need for altered force production. Muscle function relies primarily on an organized assembly of contractile and other sarcomeric proteins. From analysis of homogenized cells and molecular and biochemical assays, we have learned about transcription, translation, and posttranslational processes that underlie protein synthesis but still have done little in addressing the important questions of shape or regional cell growth. Skeletal muscles only grow in length as the bones grow; therefore, most studies of adult hypertrophy really only involve increased cross-sectional area. The heart chamber, however, can extend in both longitudinal and transverse directions, and cardiac cells can grow in length and width. We know little about the regulation of these directional processes that appear as a cell gets larger with hypertrophy or smaller with atrophy. This review gives a brief overview of the regulation of cell shape and the composition and aggregation of contractile proteins into filaments, the sarcomere, and myofibrils. We examine how mechanical activity regulates the turnover and exchange of contraction proteins. Finally, we suggest what kinds of experiments are needed to answer these fundamental questions about the regulation of muscle cell shape.


Fluids ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. 108 ◽  
Author(s):  
Junru Wu

Broadly speaking, acoustic streaming is generated by a nonlinear acoustic wave with a finite amplitude propagating in a viscid fluid. The fluid volume elements of molecules, d V , are forced to oscillate at the same frequency as the incident acoustic wave. Due to the nature of the nonlinearity of the acoustic wave, the second-order effect of the wave propagation produces a time-independent flow velocity (DC flow) in addition to a regular oscillatory motion (AC motion). Consequently, the fluid moves in a certain direction, which depends on the geometry of the system and its boundary conditions, as well as the parameters of the incident acoustic wave. The small scale acoustic streaming in a fluid is called “microstreaming”. When it is associated with acoustic cavitation, which refers to activities of microbubbles in a general sense, it is often called “cavitation microstreaming”. For biomedical applications, microstreaming usually takes place in a boundary layer at proximity of a solid boundary, which could be the membrane of a cell or walls of a container. To satisfy the non-slip boundary condition, the flow motion at a solid boundary should be zero. The magnitude of the DC acoustic streaming velocity, as well as the oscillatory flow velocity near the boundary, drop drastically; consequently, the acoustic streaming velocity generates a DC velocity gradient and the oscillatory flow velocity gradient produces an AC velocity gradient; they both will produce shear stress. The former is a DC shear stress and the latter is AC shear stress. It was observed the DC shear stress plays the dominant role, which may enhance the permeability of molecules passing through the cell membrane. This phenomenon is called “sonoporation”. Sonoporation has shown a great potential for the targeted delivery of DNA, drugs, and macromolecules into a cell. Acoustic streaming has also been used in fluid mixing, boundary cooling, and many other applications. The goal of this work is to give a brief review of the basic mathematical theory for acoustic microstreaming related to the aforementioned applications. The emphasis will be on its applications in biotechnology.


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