The method below was developed for cell shape orientation clusters and was then applied to cell trajectories to determine dynamic orientation clusters. Mol. Insets show representative dynamic packs from cells undergoing pEMT or UJT (scale bar: 100m). This loss of edge tension coincides with a solidfluid transition of the layer, at which point the shear modulus114 and energy barriers vanish (Supplementary Fig. Szabo, A. et al. Biol. Cellcell junctions become increasingly tortuous and slack. Lungs were from non-smokers with no history of chronic lung disease. Grainge, C. L. et al. b Using velocity fields obtained by optical flow and the same community-finding algorithm, cellular motions were seen to organize into oriented migratory packs. Rev. PLoS Comput. J. Clin. Negative resistance region. Upholding a role for EMT in breast cancer metastasis. A., Fredberg, J. J. In this video Working of Uni Junction Transistor(UJT) and its V-I characteristics is Explained in detail A. et al. MathSciNet Front. Open Sci. Data, both raw and analyzed, that comprise the graphs within this manuscript and other findings of this study are available from the corresponding author upon request. Source data are provided with this paper. This fitted ellipse has equivalent eigenvalues of the second area moment as of the polygon corresponding to the cell boundaries, as published previously39. 2 and 3). We establish here in the mature layer of primary HBE cells that UJT does not require pEMT. Based on dose, we found slight variations in the exact levels of epithelial and mesenchymal markers but our conclusions remain unchanged. Cell Mol. J. Appl. 3-5 2. J. In promoting collective behaviors, previous computational approaches have pointed toward the importance of cell motility, cellcell interactions, persistence, confinement, and heterogeneity43,117,118,119,120,121,122. Cell Biol. Publishers note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. We also extracted individual cell edges and computed the end-to-end distance and the contour distance along the edge to compute the edge tortuosity: Orientation clusters, or packs, were determined from both cell shape orientation and from cell trajectory orientation, using a community-finding algorithm as described below. & Thiery, J. P. Epithelialmesenchymal transitions: insights from development. The VI characteristics of UJT along with the circuit arrangement is given below. Sci. Google Scholar. Cell volume change through water efflux impacts cell stiffness and stem cell fate. Article VI characteristics in first and third quadrants are same except direction of voltage and current flow. Data presented in f are meanSD for n=89 independent simulations for each datapoint. 2d). Nat. Nat. Savagner, P. Epithelialmesenchymal transitions: from cell plasticity to concept elasticity. Primary HBE cells were isolated at Passage 0 at the Marsico Lung Institute/Cystic Fibrosis Research Center at the University of North Carolina, Chapel Hill. Phys. Cancer Cell Int. Immunofluorescent images comparing three experimental interventions across three timepoints (Fig. PubMed Central 38, e102497 (2019). 14, 10401048 (2015). First, UJT has now been observed across diverse biological systems37,38,39,41,42,43,44,45,46,47,48,49, but we do not yet know whether UJT is governed across these diverse systems by unifying biological processes or conserved signaling pathways. Sci. Cell Biol. Nat. Cai, D. et al. With emitter terminal open and a voltage VBB is applied between the two bases then the voltage drop across RB1 is given by V 1 = V B B Where = R B 1 R B 1 + R B 2 = R B 1 R B B 0 and RB1 is the Emiter-to-Base1 resistance and RB2 is the Emiter-to-Base2 resistance. During UJT, cellular cooperativity emerges and cells are able to move quickly in locally coordinated groups. Curr. Cell Sci. This conversion from sedentary to migratory behavior has traditionally been understood as a manifestation of the epithelial-to-mesenchymal transition (EMT) or the partial EMT (pEMT)5,6,7,8. CAS It has been argued, for example, that EMT-induced intermediate cell states are sufficiently rich in their confounding diversity that they cannot be captured along a linear spectrum of phenotypes flanked at its extremes by purely epithelial versus mesenchymal states5,16. 2h, Supplementary Figs. In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition, \(l_0 = v_0\tau_{\rm{{p}}}/{\mathrm{{\Gamma}}}\), $${\rm{{Tortuosity}}} = \frac{{{\rm{{contour}}}\;{\rm{{length}}}}}{{{\rm{{end - to - end}}}\;{\rm{{length}}}}}$$, \(s = (1/N_{\rm{{c}}})\mathop {\sum }\nolimits_{j = 1}^{N_{\rm{{c}}}} s_j\), https://doi.org/10.1038/s41467-020-18841-7. 3a), and exhibited undetectable or very low expression of mesenchymal markers (Fig. To induce pEMT we exposed the cell layer to TGF-1 (10ng/ml), a well-known EMT-inducing agent22,67. Henkes, S., Fily, Y. 16, 529 (2015). In well-differentiated HBE cells, 10ng/ml is an effective dose to induce hallmarks of complete EMT at 14 days (Supplementary Fig. Data presented in b and d are meanSD for n=720 independent simulations for each datapoint. & Marchetti, M. C. Active jamming: Self-propelled soft particles at high density. 3). Park, J. Cell Biol. & Thiery, J. P. Emt: 2016. It looks almost like that of the Junction Field Effect Transistor (JFET). 1c, d and 3d; Supplementary Fig. 6b, c). D 50, 483001 (2017). e Left panel: meanSEM for n=3 donors; right panel: measurements for each field of view across donors, with shape denoting each donor. https://doi.org/10.1088/1367-2630/15/7/075006. CAS PubMed EMT/pEMT refers not to a unique biological program but rather to any one of many programs, each with the capacity to confer on epithelial cells an increasingly mesenchymal character12,127. In UJT, by contrast, fluidization arises mainly from increased propulsion or persistence. Due to this . Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. ADS https://doi.org/10.1103/PhysRevX.6.021011. Peer review information Nature Communications thanks the anonymous reviewers for their contribution to the peer review of this work. J. Physiol. volume11, Articlenumber:5053 (2020) The two base contacts are attached to both ends of this N-type surface. 22, 471483 (2012). Nature 527, 525530 (2015). Neelakantan, D. et al. Vanishing edge tension in the fluidized state is consistent with the notion that EMT weakens cellcell contacts, and junctions therefore become unable to support mechanical forces. Zheng, X. et al. 37, 169185 (2007). See also Supplementary Table1 and online Source Data file. Invest. The epithelial-to-mesenchymal transition (EMT) and the unjamming transition (UJT) each comprises a gateway to cellular migration, plasticity and remodeling, but the extent to which these core programs are distinct, overlapping, or identical has remained undefined. Simultaneously, the speed of the cell migration increases (inset). Park, J. The inter base resistance R BB of the N-type Si bar appears as two resistors R B1 and R B2. EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. CAS Semin. Google Scholar. interpreted data; J.A.M., A.D., J.J.F., D.B., J.-A.P. & Heisenberg, C. P. Tissue rheology in embryonic organization. 1. CAS Glass, K. et al. X 9, 011029 (2019). A. et al. CAS & Nieto, M. A. A. Cell Biol. Insets show traced cell edges from representative images of cells in each state. Moreover, EMT/pEMT is associated with the cells of highly aggressive tumors, endows cancer cells with stemness and resistance to cytotoxic anticancer drugs, and may be required in the fibrotic response21,22. J. Med. A., Fredberg, J. J. 130, 13751383 (2012). J. We then used DVM to better understand emergence of collective behavior during UJT (Fig. 5, 155 (2015). 2f, Supplementary Fig. 2ac). For each biological replicate used to obtain structural measurements, two fields of view were taken, from which ~2000 cells were evaluated. These pathologic responses include asthmatic airway remodeling81,82,83,84,85,86,87,88,89,90 and a robust UJT37,38,39. The Unijunction Transistor or UJT for short, is another solid state three terminal device that can be used in gate pulse, timing circuits and . Ross, A. J., Dailey, L. A., Brighton, L. E. & Devlin, R. B. Transcriptional profiling of mucociliary differentiation in human airway epithelial cells. Oswald, L., Grosser, S., Smith, D. M. & Ks, J. While poorly understood, cellular jamming and unjamming have been identified in epithelial systems in vitro37,39,43,46,48,49,54,55,56, in developmental systems in vivo39,42,50,57,58,59, and have been linked to the pathobiology of asthma37,38,39 and cancer45,47,60,61. (1985) 66, 28732884 (1989). Biol. The forward and reverse operating conditions or ON and OFF states of UJT depends on the emitter voltage V E, Similar To CE With A Linear And Saturation Region 2. The P-N junction is reverse biased and emitter current I E is negative as long as the emitter voltage V E < V BB as shown by the curve PS. Slides were imaged using Zen Blue 2.0 software on a Zeiss Axio Observer Z1 using an apotome module. Adhesion forces and cortical tension couple cell proliferation and differentiation to drive epidermal stratification. Pastushenko, I. 18, 13111323 (2016). 3). Development, wound repair, and cancer metastasis are fundamental biological processes. Sci. This dose of TGF-1 was chosen according to a dose-dependent experiment at 1, 10, and 50ng/ml, at which EMT is induced in a variety of systems145,146,147,148,149. Heer, N. C. et al. Am. Cell Motil. CAS PubMed Central Chronic intermittent mechanical stress increases MUC5AC protein expression. 4a). Hackett, T. L. et al. We wish to emphasize, however, that these approaches often impose on an ad hoc basis a local penalty when any given cell fails to align with its immediate neighbors49,121,122,123,124. PubMed Central More generally, forces applied locally or generated endogenously are known to initiate biochemical signaling, cellular deformation and migration78,79,80. Article 240, 15021511 (2011). Second, based upon simple physical arguments this level of compressive stress is readily generalizable to other situations For example, the bulk compressive stiffness modulus of the cell is quite largeon the order of 107108Pa whereas traction stresses are typically on the order of 100Pa, intercellular stresses are on the order of 1000Pa, cellular Youngs moduli vary from 100Pa to 10kPa depending on cell type74, and the cortical shear stiffness is on the order of 1000Pa37,75,76,77. Experiments were repeated with primary cells from at least n=34 donors in independent experiments. That consensus emphasizes that EMT status cannot be assessed solely on the basis of a single or even a small number of molecular markers. Mater. c If p0 is moderate (p0=4) and propulsive force v0 is small the cell layer is immobile (iv). Mater. Similar To PN Junction Diode In Some Respects Hide Explanation Answer.3. Chem. FN-EDA and vimentin appear during pEMT but not UJT. Ilina, O. et al. In the process, epithelial barrier function becomes compromised. To account for these striking physical observations a new computational model attributes the effects of pEMT mainly to diminished junctional tension but attributes those of UJT mainly to augmented cellular propulsion. Matsubayashi, Y., Ebisuya, M., Honjoh, S. & Nishida, E. ERK activation propagates in epithelial cell sheets and regulates their migration during wound healing. Zhang, J. et al. (1) Potentiometer - 10k \ ( \Omega \) 3. Beerling, E. et al. Cells were counterstained with Hoechst 33342 (1:5000) for nuclei. As such, EMT likely evolved as a mechanism that allows individual epithelial cells or cell clusters to separate from neighbors within the cell layer and thereafter invade and migrate through adjacent tissue132. Top. Interface 9, 32683278 (2012). V E is positive with respect B1. Cell density and actomyosin contractility control the organization of migrating collectives within an epithelium. Lung Cell. & Levine, H. EMT and MET: necessary or permissive for metastasis? Sci. 1d, e, Supplementary Table1). Mongera, A. et al. V E is positive with respect B1. Access ports were either open to room air for sham controls or connected to 5% CO2 (balanced room air) compressed to 30cm H2O. Biol. Google Scholar. Kalluri, R. & Weinberg, R. A. wrote the manuscript. Pawlizak, S. et al. It resembles to that of the diode with a single junction of the P-N. More broadly, the Human Lung Cell Atlas now points not only to dramatic heterogeneities of airway cells and cell states, but also to strong proximal-to-distal gradients along the airway tree141. Aoki, K. et al. Oncol. 14, 613620 (2018). 1d) were repeated in n=4 donors while structural measurements (Figs. Control HBE cells were essentially stationary, as if frozen in place, exhibiting only occasional small local motions which were insufficient for cells to uncage or perform local rearrangements with their immediate neighbors (Fig. Liu, A. J. & Weinberg, R. A. Rev. 1. Demographic information is available for all donors used in our study upon request. Tschumperlin, D. J. et al. Give the VI characteristics of UJT. Mater. This energy, in turn, derives from three main contributions: deformability of the cytoplasm and associated changes of cell area; contractility of the apical actin ring and associated changes of its perimeter; and homotypic binding of cellcell adhesion molecules, such as cadherins, together with extensibility of attendant contractile elements and associated changes in cell perimeter37,109,110. PLoS Comput. The basics of epithelialmesenchymal transition. 25, 38733883 (2011). In this process each epithelial cell tends to free itself from adhesions to immediate neighbors, and thereby can acquire migratory capacity and invasiveness. 1ac). Nat. These structures and associated energies, taken together, lead to a preferred cell perimeter, p0, and determine the tension borne along the cellcell junction, here called edge tension37,109,110. Biol. Correspondence to 6-8 3 To plot and study the input and output characteristics of BJT in common-emitter configuration. PubMed 144, 11161118 e1114 (2019). After triggering UJT, cell-cell junctions, apico-basal polarity, and barrier function remain intact, cells elongate and align into cooperative migratory packs, and mesenchymal markers of EMT remain unapparent. Nnetu, K. D., Knorr, M., Pawlizak, S., Fuhs, T. & Ks, J. & Fredberg, J. J. While the precise dynamic and structural characteristics of the HBE layer undergoing pEMT have not been previously explored, UJT is known to be marked by the onset of stochastic but cooperative migratory dynamics together with systematic elongation of cell shapes37,38,39,49,91,92. Exposure to TGF-1 (10ng/ml) disrupted epithelial architecture and led to acquisition of mesenchymal character (Fig. This loss of epithelial character is accompanied by progressive gain of mesenchymal character, including gain of frontback polarity, activation of EMT-inducing transcription factors, and expression of mesenchymal markers11,12. PubMed Central A Unijunction Transistor (UJT) is a three-terminal semiconductor device. 285, 2981729825 (2010). Physiol. performed dynamic vertex model simulations; J.A.M., A.D., M.J.O., S.K., D.B. Sine Wave 2. To Study the characteristics of transistor in Common Base configuration. PubMed Cell Biol. EMT is marked by progressive loss of epithelial character, including disrupted apico-basal polarity, disassembled cellcell junctions, and impaired epithelial layer integrity and barrier function. Unlike those underlying EMT12, molecular mechanisms of UJT are largely unexplored. 2b, c and3b, d). Article Determine the frequency of oscillations. Nat. 154, 820 (1995). 2d), suggesting that cellcell junctions were under the influence of mechanical line tension93,94. Biol. Angelini, T. E. et al. 5b) and functional measurements (Fig. Segmented images were used to determine cell boundaries and extract cell shape information, including apical cell area, perimeter, and AR from major and minor axes of an equivalent ellipse. Cell Biol. 4f and5b). Google Scholar. Ng, M. R., Besser, A., Danuser, G. & Brugge, J. S. Substrate stiffness regulates cadherin-dependent collective migration through myosin-II contractility. 17, 20952104 (2007). These authors contributed equally: Jennifer A. Mitchel, Amit Das. Nat. Let increasing this voltage from zero. Kabla, A. J. Airway epithelial compression promotes airway smooth muscle proliferation and contraction. Cut-off region Negative . Proc. 2d)93,94. Cellular dynamics were determined using an optical flow algorithm. Mixed epithelial and mesenchymal characteristics, and the interactions between them, are thought to be essential for carcinoma cell invasion and dissemination 13,14,16,20,120, but how UJT might . EMT subtype influences epithelial plasticity and mode of cell migration. However, the time evolution of median pack size and speed from cells undergoing UJT (blue squares) are consistent with these predictions. Thus, for the entire culture period, HBE cells were maintained in defined, serum-free media81. Although pEMT has been defined inconsistently in the literature, this dose has been established to induce pEMT in HBE cells in ALI culture67, a result borne out by our experiments and in line with the criteria defined in a recent consensus statement on EMT12. 315, L645L652 (2018). In the jammed phase, the motion of each individual cell tends to be caged by its nearest neighbors. 11, 10741079 (2015). Rev. Top. Each cell is shown with an orientation director whose length is proportional to AR. 1. Yan, L. & Bi, D. Multicellular rosettes drive fluidsolid transition in epithelial tissues. Mater. CAS c Cells did not exhibit large structural packs when jammed or during pEMT at any time point. *p<0.05, vs. control; #p<0.05, pEMT vs. UJT, color-coded according to which sample is referenced, one-way ANOVA followed by post-hoc multiple comparisons test with Bonferroni correction d, e. f During pEMT, cortical actin becomes disrupted while apical stress fibers emerge, indicating loss of epithelial character and gain of mesenchymal character. Immunol. 2) To find Latching and Holding current of the given SCR. Individual data points for each donor are shown. Piacentino, M. L., Li, Y. Respirology 24, 10731080 (2019). Acta Anat. Eng. Front. & Weinberg, R. A. EMT in cancer. Biophys. Nat. 1 and 2. a In both jammed and UJT layers, ZO-1 (red) localizes at apical tight junctions, while E-cadherin (green) localizes at lateral adherens junctions, consistent with the epithelial phenotype; DNA is shown in blue. During UJT, these protein levels remained unchanged. X 10, 011016 (2020). Effect of bronchoconstriction on airway remodeling in asthma. As a time-matched positive control for pEMT we used the cell layer subjected to graded concentrations of TGF-1 (see Methods section). Article 1a, b and 3d). Yager, D. et al. Cell shapes become progressively elongated but cell edges remain straight (panels ivvi). Atia, L. et al. Nat Commun 11, 5053 (2020). *p<0.05, vs. control; #p<0.05, UJT vs. pEMT, color-coded according to which sample is referenced, one-way ANOVA followed by post-hoc multiple comparisons with Bonferroni correction. Barriga, E. H. & Mayor, R. Adjustable viscoelasticity allows for efficient collective cell migration. Opin. 2, Supplementary Figs. In HBE cells undergoing pEMT, these data serve as a positive control for loss of epithelial character and gain of mesenchymal character. Cells also acquired increased expression of EMT-inducing transcription factors including Zeb1 and Snail1, and mesenchymal markers including N-cadherin, vimentin, and fibronectin (EDA isoform) (Fig. 10. Google Scholar. Harvard T.H. As p0 progressively increases cell shapes become elongated (ii) and cell edges become increasingly tortuous, as if slackened (iii). By contrast to cells during pEMT, cells during UJT did not gain a detectable mesenchymal molecular signature (Fig. In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition. 27 7K views 4 years ago How to Simulate UJT Characteristics with Multisim Software. Cell Stem Cell 26, 482502 (2020). Protein measurements (Fig. Small - signal amplifier 2. . 1. Cancer 18, 296312 (2018). Over 1417 days in ALI, the cells differentiated and formed a pseudostratified epithelium which recapitulated the cellular architecture and constituency of the intact human airway39,63,64,86,144. Nat. & Montell, D. J. 2gi, Supplementary Fig. New J. Phys. Each cell or trajectory possessed orientation j with respect to a global axis of reference. Phys. Condens. Google Scholar. The Human Lung Cell Atlasa high-resolution reference map of the human lung in health and disease. B 375, 20190391 (2020). NATURE OF GRAPH: V.I.Characteristics of SCR : Pin configuration of SCR: Expt.No.1 STATIC CHARACTERISTICS OF SCR AIM: 1) To plot the static characteristics of the given SCR. Campbell, K. & Casanova, J. Mol. A null test for our algorithm was to set =90 and find that all cells in an image became part of the same connected cluster giving a mean pack-size equal to the number of cells. Due to this characteristic feature, it is used in applications like switching pulse generator, saw-tooth wave generator etc. Giavazzi, F. et al. & Bronner, M. E. Epithelial-to-mesenchymal transition and different migration strategies as viewed from the neural crest. Dev. 109, 14951509 (1989). ADS Due to the presence of a non-degradable basal transwell-insert, epithelial cells in our system cannot invade, and thus we could not compare invasion phenotypes between UJT and pEMT. Biol. https://doi.org/10.1242/dev.175257. In the DVM, increasing p0 mimics well progressive disruption of the cellcell-junction and is thus seen to reflect the known physical effects of pEMT (Fig. Ques.33. i During pEMT, mRNA expression of mesenchymal markers, shown as fold-change relative control, VIM and FN-EDA and the EMT-inducing TF ZEB1, are significantly elevated, but during UJT remain unchanged. The linear sizes of the packs are measured relative to the size of the simulation window (Supplementary Methods). 9, a029199 (2017). Park, J. Genet. Tetley, R. J. et al. For experiments with time points longer than 24h, cells were fed with fresh minimal media at 48h following the initial media change prior to exposure. Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Importantly, the transition through pEMT to full EMT strongly varies depending on both the degree and the duration of the EMT-initiating signal. 15, 075006 (2013). In each process cells of epithelial origin are ordinarily sedentary but can become highly migratory. Rev. With emitter terminal open and a voltage VBB is applied between the two bases then the voltage drop across RB1 is given by V 1 = V B B Where = R B 1 R B 1 + R B 2 = R B 1 R B B 0 and RB1 is the Emiter-to-Base1 resistance and RB2 is the Emiter-to-Base2 resistance. Unijunction Transistor. Nat. The single-junction transistor (UJT) will be used as a voltage separation device. & Miller, R. T. Mechanisms of mechanical signaling in development and disease. Han, Y. L. et al. iii. We detected the number of neighbors mi of the ith cell possessed similar orientations within a cutoff =10. J. Anat. La Porta, C. A. M. & Zapperi, S. Phase transitions in cell migration. 2ac, f, g and Supplementary Figs. 2d). Article To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Nat. Trans. low energy) elastic mechanical modes become available to the system as opposed to the high-frequency modes which are associated with localized rearrangements. Nat. Biochem. 5a). During UJT, by contrast, cells aligned into packs whose median size progressively grew in cell number from 24 to 72h. Left panel: meanSEM for n=3 donors; right panel: measurements for each donor, delineated by symbol shape. Cell Mol. Tian, B. et al. The V I Characteristics of UJT (unijunction transistor) is show in above fig. This was followed by a post-hoc analysis using a Bonferroni correction, and p<0.05 was considered significant. To better understand underlying mechanical factors that differentiate pEMT versus UJT, we extend previous computational analyses based on so-called vertex models37,39,91,92,109,110,111,112. Bi, D., Lopez, J. H., Schwarz, J. M. & Manning, M. L. Energy barriers and cell migration in densely packed tissues. Nieto, M. A. Context-specific roles of EMT programmes in cancer cell dissemination. During pEMT edge tension decreases as junctional adhesion decreases, and as cells elongate q increases more quickly than AR. Development 146, dev175257 (2019). 2ac, 3a, b) were not quantified. 3. 124, 188197 (2002). Nonetheless, our data are consistent with the hypothesis that UJT might have evolved as a mechanism that allows epithelial rearrangements, migration, remodeling, plasticity, or development within a tissue under the physiological constraint of preserving tissue continuity, integrity, and barrier function. During UJT, by contrast, edge tension increases as cellular propulsion v0 increases, AR and q increase in tandem, and cells elongate. 80, 076601 (2017). The following antibodies and dilutions were used, with primary antibody diluted in 5% skim milk or 5% BSA according to the manufacturers instructions: E-cadherin (1:10,000), N-cadherin (1:1000), Snail1 (1:1000), vimentin (1:1000), GAPDH (1:5000), all from Cell Signaling Technology; EDA-fibronectin (1:1000, Sigma). A. et al. Indeed, we found that blocking ERK activity using the pharmacological inhibitor U0126 (10M)81,99 attenuated compression-induced cellular motility, thus confirming that ERK signaling is required for compression-induced UJT(Supplementary Fig. Heer, N. C. & Martin, A. C. Tension, contraction and tissue morphogenesis. 1d, e). Opin. If the input is used between the emitter and base 1, the minimum value of the interval will be reduced, that is, R B1 will rise to a higher value. Western blot quantification shown in Supplementary Figs. To mark cellular boundaries, we segmented immunofluorescent cell images using SeedWater Segmenter (v0.5.7.1)13. J. Savagner, P. et al. Trends Cell Biol. J. Respir. Cell Biol. Dvorak, A., Tilley, A. E., Shaykhiev, R., Wang, R. & Crystal, R. G. Do airway epithelium air-liquid cultures represent the in vivo airway epithelium transcriptome? Irradiation induces epithelial cell unjamming. A few include oscillators, trigger circuits, saw-tooth generators, bistable network etc. Immunol. Ressler, B., Lee, R. T., Randell, S. H., Drazen, J. M. & Kamm, R. D. Molecular responses of rat tracheal epithelial cells to transmembrane pressure. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Phys. Shellard, A. Am. Primary HBE cells at passage 2 were differentiated in ALI, described below37,81,83,84,85. Chiou, K. K., Hufnagel, L. & Shraiman, B. I. Propagating wave of ERK activation orients collective cell migration. 22, 11031115 (2020). Using the confluent layer of HBE cells, we trigger UJT by exposing the sedentary layer to a mechanical stress that has been tightly linked to aberrant remodeling of the asthmatic airway37,38,39,66. Images were taken every 6min for 6h, ending at 24, 48, or 72h after initial exposure to stimuli. In both the solid-like jammed phase and the fluid-like unjammed phase, the epithelial collective retains an amorphous disordered structure. Cells thereafter migrate cooperatively, align into packs locally, and elongate systematically. 4e, f and 5b). The largest migrating packs are also shown (green triangles), which grow to the size of the simulation window for l0>100, highlighting the scalability and robustness of pack formation in DVM. Google Scholar. & Nagel, S. R. Jamming transition and marginally jammed solid. 4b). Every organ surface and body cavity is lined by a confluent collective of epithelial cells. 3b, c). During pEMT dynamic packs were substantially larger at 24h but returned to baseline by 48h. During UJT, by contrast, dynamic packs grew dramatically in size and remained elevated out to 72h. Left panel: meanSEM for n=4 donors; right panel: measurements for each donor, delineated by symbol shape. 138, 477488 (2012). Curr. 150, 200901 (2019). Edge tortuosity can arise in regions where the effects of edge tension becomes small compared with intracellular pressure differences between adjacent cells.
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