From coffee beans flowing in a chute to cells remodelling in a living tissue, a wide variety of close-packed collective systems—both inert and living—have the potential to jam. The collective can sometimes flow like a fluid or jam and rigidify like a solid. The unjammed-to-jammed transition remains poorly understood, however, and structural properties characterizing these phases remain unknown. Using primary human bronchial epithelial cells, we show that the jamming transition in asthma is linked to cell shape, thus establishing in that system a structural criterion for cell jamming. Surprisingly, the collapse of critical scaling predicts a counter-intuitive relationship between jamming, cell shape and cell–cell adhesive stresses that is borne out by direct experimental observations. Cell shape thus provides a rigorous structural signature for classification and investigation of bronchial epithelial layer jamming in asthma, and potentially in any process in disease or development in which epithelial dynamics play a prominent role.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Scientific Reports Open Access 21 June 2023
Nature Physics Open Access 06 April 2023
Nature Communications Open Access 13 February 2023
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Holgate, S. T. Pathogenesis of asthma. Clin. Exp. Allergy 38, 872–897 (2008).
Friedl, P. & Gilmour, D. Collective cell migration in morphogenesis, regeneration and cancer. Nature Rev. Mol. Cell Biol. 10, 445–457 (2009).
Henkes, S., Fily, Y. & Marchetti, M. C. Active jamming: Self-propelled soft particles at high density. Phys. Rev. E 84, 040301 (2011).
Tambe, D. T. et al. Collective cell guidance by cooperative intercellular forces. Nature Mater. 10, 469–475 (2011).
Haeger, A., Krause, M., Wolf, K. & Friedl, P. Cell jamming: Collective invasion of mesenchymal tumor cells imposed by tissue confinement. Biochim. Biophys. Acta 1840, 2386–2395 (2014).
Thiery, J. P., Acloque, H., Huang, R. Y. & Nieto, M. A. Epithelial–mesenchymal transitions in development and disease. Cell 139, 871–890 (2009).
Banigan, E. J., Illich, M. K., Stace-Naughton, D. J. & Egolf, D. A. The chaotic dynamics of jamming. Nature Phys. 9, 288–292 (2013).
Kim, J. H. et al. Propulsion and navigation within the advancing monolayer sheet. Nature Mater. 12, 856–863 (2013).
Nnetu, K., Knorr, M., Pawlizak, S., Fuhs, T. & Käs, J. A. Slow and anomalous dynamics of an MCF-10A epithelial cell monolayer. Soft Matter 9, 9335–9341 (2013).
Trepat, X. et al. Physical forces during collective cell migration. Nature Phys. 5, 426–430 (2009).
Berthier, L. Nonequilibrium glassy dynamics of self-propelled hard disks. Phys. Rev. Lett. 112, 220602 (2014).
Park, J. A. & Tschumperlin, D. J. Chronic intermittent mechanical stress increases MUC5AC protein expression. Am. J. Respir. Cell Mol. Biol. 41, 459–466 (2009).
Gray, T. E., Guzman, K., Davis, C. W., Abdullah, L. H. & Nettesheim, P. Mucociliary differentiation of serially passaged normal human tracheobronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 14, 104–112 (1996).
Tschumperlin, D. J. et al. Mechanotransduction through growth-factor shedding into the extracellular space. Nature 429, 83–86 (2004).
Grainge, C. L. et al. Effect of bronchoconstriction on airway remodeling in asthma. N. Engl. J. Med. 364, 2006–2015 (2011).
Angelini, T. E. et al. Glass-like dynamics of collective cell migration. Proc. Natl Acad. Sci. USA 108, 4714–4719 (2011).
Sadati, M., Taheri Qazvini, N., Krishnan, R., Park, C. Y. & Fredberg, J. J. Collective migration and cell jamming. Differentiation 86, 121–125 (2013).
Farhadifar, R., Roper, J. C., Aigouy, B., Eaton, S. & Julicher, F. The influence of cell mechanics, cell–cell interactions, and proliferation on epithelial packing. Curr. Biol. 17, 2095–2104 (2007).
Bi, D., Lopez, J., Schwarz, J. & Manning, M. L. A density-independent glass transition in biological tissues. Preprint at http://arXiv.org/abs/1409.0593v1 (2014).
Bi, D., Lopez, J. H., Schwarz, J. M. & Manning, M. L. Energy barriers and cell migration in densely packed tissues. Soft Matter 10, 1885–1890 (2014).
Wiggs, B. R., Hrousis, C. A., Drazen, J. M. & Kamm, R. D. On the mechanism of mucosal folding in normal and asthmatic airways. J. Appl. Phys. 83, 1814–1821 (1997).
Gunst, S. J. & Stropp, J. Q. Pressure–volume and length–stress relationships in canine bronchi in vitro. J. Appl. Phys. 64, 2522–2531 (1988).
Keys, A., Abate, A., Glotzer, S. C. & Durian, D. J. Measurement of growing dynamical length scales and prediction of the jamming transition in granular material. Nature Phys. 3, 260–264 (2007).
Berthier, L. et al. Direct experimental evidence of a growing length scale accompanying the glass transition. Science 310, 1797–1800 (2005).
Weeks, E. R., Crocker, J. C., Levitt, A. C., Schofield, A. & Weitz, D. A. Three-dimensional direct imaging of structural relaxation near the colloidal glass transition. Science 287, 627–631 (2000).
Garrahan, J. P. Dynamic heterogeneity comes to life. Proc. Natl Acad. Sci. USA 108, 4701–4702 (2011).
Abate, A. R. & Durian, D. J. Topological persistence and dynamical heterogeneities near jamming. Phys. Rev. E 76, 021306 (2007).
Angell, C. A. Formation of glasses from liquids and biopolymers. Science 267, 1924–1935 (1995).
Damera, G. et al. Ozone modulates IL-6 secretion in human airway epithelial and smooth muscle cells. Am. J. Physiol. Lung Cell Mol. Physiol. 296, L674–L683 (2009).
Xiao, C. et al. Defective epithelial barrier function in asthma. J. Allergy Clin. Immunol. 128, 549–556 (2011).
Roth, H. M., Wadsworth, S. J., Kahn, M. & Knight, D. A. The airway epithelium in asthma: Developmental issues that scar the airways for life? Pulm. Pharmacol. Ther. 25, 420–426 (2012).
Trappe, V., Prasad, V., Cipelletti, L., Segre, P. N. & Weitz, D. A. Jamming phase diagram for attractive particles. Nature 411, 772–775 (2001).
Liu, A. J. & Nagel, S. R. Jamming is not just cool any more. Nature 396, 21–22 (1998).
Park, J. A., Drazen, J. M. & Tschumperlin, D. J. The chitinase-like protein YKL-40 is secreted by airway epithelial cells at base line and in response to compressive mechanical stress. J. Biol. Chem. 285, 29817–29825 (2010).
Hardyman, M. A. et al. TNF-α-mediated bronchial barrier disruption and regulation by src-family kinase activation. J. Allergy Clin. Immunol. 132, 665–672 (2013).
Tambe, D. T. et al. Monolayer stress microscopy: Limitations, artifacts, and accuracy of recovered intercellular stresses. PLoS ONE 8, e55172 (2013).
Bazellieres, E. et al. Control of cell–cell forces and collective cell dynamics by the intercellular adhesome. Nature Cell Biol. 17, 409–420 (2015).
Glazier, J. A. & Graner, F. Simulation of the differential adhesion driven rearrangement of biological cells. Phys. Rev. E 47, 2128–2154 (1993).
Brodland, G. W. The differential interfacial tension hypothesis (DITH): A comprehensive theory for the self-rearrangement of embryonic cells and tissues. J. Biomech. Eng. 124, 188–197 (2002).
Steward, R., Tambe, D. Jr, Hardin, C. C., Krishnan, R. & Fredberg, J. J. Fluid shear, intercellular stress, and endothelial cell alignment. Am. J. Physiol. Cell Physiol. 308, C657–C664 (2015).
Yang, X., Manning, M. L. & Marchetti, M. C. Aggregation and segregation of confined active particles. Soft Matter 10, 6477–6484 (2014).
Basan, M., Elgeti, J., Hannezo, E., Rappel, W. J. & Levine, H. Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing. Proc. Natl Acad. Sci. USA 110, 2452–2459 (2013).
Sepulveda, N. et al. Collective cell motion in an epithelial sheet can be quantitatively described by a stochastic interacting particle model. PLoS Comput. Biol. 9, e1002944 (2013).
Szabo, A. et al. Collective cell motion in endothelial monolayers. Phys. Biol. 7, 046007 (2010).
Kabla, A. J. Collective cell migration: Leadership, invasion and segregation. J. R. Soc. Interface 9, 3268–3278 (2012).
Li, B. & Sun, S. X. Coherent motions in confluent cell monolayer sheets. Biophys. J. 107, 1532–1541 (2014).
Attanasi, A. et al. Finite-size scaling as a way to probe near-criticality in natural swarms. Phys. Rev. Lett. 113, 238102 (2014).
Fredberg, J. J. Power steering, power brakes, and jamming: Evolution of collective cell–cell interactions. Physiology 29, 218–219 (2014).
Hidalgo, J. et al. Information-based fitness and the emergence of criticality in living systems. Proc. Natl Acad. Sci. USA 111, 10095–10100 (2014).
Lazaar, A. L. & Panettieri, R. A. Jr Is airway remodeling clinically relevant in asthma? Am. J. Med. 115, 652–659 (2003).
Swartz, M. A., Tschumperlin, D. J., Kamm, R. D. & Drazen, J. M. Mechanical stress is communicated between different cell types to elicit matrix remodeling. Proc. Natl Acad. Sci. USA 98, 6180–6185 (2001).
Park, J. A. et al. Tissue factor-bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo. J. Allergy Clin. Immunol. 130, 1375–1383 (2012).
Trepat, X. et al. Universal physical responses to stretch in the living cell. Nature 447, 592–595 (2007).
Serra-Picamal, X. et al. Mechanical waves during tissue expansion. Nature Phys. 8, 628–634 (2012).
Angelini, T. E., Hannezo, E., Trepat, X., Fredberg, J. J. & Weitz, D. A. Cell migration driven by cooperative substrate deformation patterns. Phys. Rev. Lett. 104, 168104 (2010).
Butler, J. P., Tolic-Norrelykke, I. M., Fabry, B. & Fredberg, J. J. Traction fields, moments, and strain energy that cells exert on their surroundings. Am. J. Physiol. Cell Physiol. 282, C595–C605 (2002).
Efron, B. & Tibshirani, R. An Introduction to the Bootstrap (Chapman & Hall, 1993).
Authors thank the staff of the UNC CF Center, Tissue Procurement and Cell Culture Core at the University of North Carolina, Chapel Hill. This research was supported by the Francis Family Foundation, the Alfred P. Sloan Foundation, the American Heart Association (13SDG14320004), the National Research Foundation of Korea (NRF-2013S1A2A2035518), the National Science Foundation (BMMB-1334611, DMR-1352184) and the National Institutes of Health (K25HL091124, P30DK065988, P30ES000002, HL007118, R01HL102373, R01HL107561, P01HL120839).
The authors declare no competing financial interests.
Supplementary Information (PDF 1953 kb)
Supplementary Movie 1 (MOV 7193 kb)
Supplementary Movie 2 (MOV 8065 kb)
Supplementary Movie 3 (MOV 12679 kb)
Supplementary Movie 4 (MOV 31176 kb)
About this article
Cite this article
Park, JA., Kim, J., Bi, D. et al. Unjamming and cell shape in the asthmatic airway epithelium. Nature Mater 14, 1040–1048 (2015). https://doi.org/10.1038/nmat4357
This article is cited by
Scientific Reports (2023)
Nature Communications (2023)
Nature Physics (2023)
Nature Materials (2023)
α-catenin switches between a slip and an asymmetric catch bond with F-actin to cooperatively regulate cell junction fluidity
Nature Communications (2022)