Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Unjamming and cell shape in the asthmatic airway epithelium


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: In a confluent layer of well-differentiated HBECs, compressive stress mimicking bronchospasm, as in asthmatic bronchospasm, provokes the transition from a solid-like jammed phase to a fluid-like unjammed phase.
Figure 2: In HBECs over the course of ALI culture, a spontaneous phase transition occurs from a hypermobile, unjammed, fluid-like phase into a quiescent, jammed, solid-like phase, which was delayed in cells from asthmatic donors.
Figure 3: In HBECs derived from asthmatic donors compared with those from non-asthmatic donors, tractions and intercellular stresses are greater but the spatial correlation of tension decays faster.
Figure 4: With increasing maturation of HBECs in ALI culture, cell perimeter, as expressed by the non-dimensional parameter , decreases systematically towards the critical value p0 (3.81) predicted to occur at jamming by the vertex model together with the theory of critical scaling exponents.


  1. 1

    Holgate, S. T. Pathogenesis of asthma. Clin. Exp. Allergy 38, 872–897 (2008).

    Article  CAS  Google Scholar 

  2. 2

    Friedl, P. & Gilmour, D. Collective cell migration in morphogenesis, regeneration and cancer. Nature Rev. Mol. Cell Biol. 10, 445–457 (2009).

    Article  CAS  Google Scholar 

  3. 3

    Henkes, S., Fily, Y. & Marchetti, M. C. Active jamming: Self-propelled soft particles at high density. Phys. Rev. E 84, 040301 (2011).

    Google Scholar 

  4. 4

    Tambe, D. T. et al. Collective cell guidance by cooperative intercellular forces. Nature Mater. 10, 469–475 (2011).

    Article  CAS  Google Scholar 

  5. 5

    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).

    Article  CAS  Google Scholar 

  6. 6

    Thiery, J. P., Acloque, H., Huang, R. Y. & Nieto, M. A. Epithelial–mesenchymal transitions in development and disease. Cell 139, 871–890 (2009).

    Article  CAS  Google Scholar 

  7. 7

    Banigan, E. J., Illich, M. K., Stace-Naughton, D. J. & Egolf, D. A. The chaotic dynamics of jamming. Nature Phys. 9, 288–292 (2013).

    Article  CAS  Google Scholar 

  8. 8

    Kim, J. H. et al. Propulsion and navigation within the advancing monolayer sheet. Nature Mater. 12, 856–863 (2013).

    Article  CAS  Google Scholar 

  9. 9

    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).

    Article  CAS  Google Scholar 

  10. 10

    Trepat, X. et al. Physical forces during collective cell migration. Nature Phys. 5, 426–430 (2009).

    Article  CAS  Google Scholar 

  11. 11

    Berthier, L. Nonequilibrium glassy dynamics of self-propelled hard disks. Phys. Rev. Lett. 112, 220602 (2014).

    Article  CAS  Google Scholar 

  12. 12

    Park, J. A. & Tschumperlin, D. J. Chronic intermittent mechanical stress increases MUC5AC protein expression. Am. J. Respir. Cell Mol. Biol. 41, 459–466 (2009).

    Article  CAS  Google Scholar 

  13. 13

    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).

    Article  CAS  Google Scholar 

  14. 14

    Tschumperlin, D. J. et al. Mechanotransduction through growth-factor shedding into the extracellular space. Nature 429, 83–86 (2004).

    Article  CAS  Google Scholar 

  15. 15

    Grainge, C. L. et al. Effect of bronchoconstriction on airway remodeling in asthma. N. Engl. J. Med. 364, 2006–2015 (2011).

    Article  CAS  Google Scholar 

  16. 16

    Angelini, T. E. et al. Glass-like dynamics of collective cell migration. Proc. Natl Acad. Sci. USA 108, 4714–4719 (2011).

    Article  Google Scholar 

  17. 17

    Sadati, M., Taheri Qazvini, N., Krishnan, R., Park, C. Y. & Fredberg, J. J. Collective migration and cell jamming. Differentiation 86, 121–125 (2013).

    Article  CAS  Google Scholar 

  18. 18

    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).

    Article  CAS  Google Scholar 

  19. 19

    Bi, D., Lopez, J., Schwarz, J. & Manning, M. L. A density-independent glass transition in biological tissues. Preprint at (2014).

  20. 20

    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).

    Article  CAS  Google Scholar 

  21. 21

    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).

    CAS  Google Scholar 

  22. 22

    Gunst, S. J. & Stropp, J. Q. Pressure–volume and length–stress relationships in canine bronchi in vitro. J. Appl. Phys. 64, 2522–2531 (1988).

    CAS  Google Scholar 

  23. 23

    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).

    Article  CAS  Google Scholar 

  24. 24

    Berthier, L. et al. Direct experimental evidence of a growing length scale accompanying the glass transition. Science 310, 1797–1800 (2005).

    Article  CAS  Google Scholar 

  25. 25

    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).

    Article  CAS  Google Scholar 

  26. 26

    Garrahan, J. P. Dynamic heterogeneity comes to life. Proc. Natl Acad. Sci. USA 108, 4701–4702 (2011).

    Article  Google Scholar 

  27. 27

    Abate, A. R. & Durian, D. J. Topological persistence and dynamical heterogeneities near jamming. Phys. Rev. E 76, 021306 (2007).

    CAS  Google Scholar 

  28. 28

    Angell, C. A. Formation of glasses from liquids and biopolymers. Science 267, 1924–1935 (1995).

    Article  CAS  Google Scholar 

  29. 29

    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).

    Article  CAS  Google Scholar 

  30. 30

    Xiao, C. et al. Defective epithelial barrier function in asthma. J. Allergy Clin. Immunol. 128, 549–556 (2011).

    Article  CAS  Google Scholar 

  31. 31

    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).

    CAS  Google Scholar 

  32. 32

    Trappe, V., Prasad, V., Cipelletti, L., Segre, P. N. & Weitz, D. A. Jamming phase diagram for attractive particles. Nature 411, 772–775 (2001).

    Article  CAS  Google Scholar 

  33. 33

    Liu, A. J. & Nagel, S. R. Jamming is not just cool any more. Nature 396, 21–22 (1998).

    Article  CAS  Google Scholar 

  34. 34

    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).

    Article  CAS  Google Scholar 

  35. 35

    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).

    Article  CAS  Google Scholar 

  36. 36

    Tambe, D. T. et al. Monolayer stress microscopy: Limitations, artifacts, and accuracy of recovered intercellular stresses. PLoS ONE 8, e55172 (2013).

    Article  CAS  Google Scholar 

  37. 37

    Bazellieres, E. et al. Control of cell–cell forces and collective cell dynamics by the intercellular adhesome. Nature Cell Biol. 17, 409–420 (2015).

    Article  CAS  Google Scholar 

  38. 38

    Glazier, J. A. & Graner, F. Simulation of the differential adhesion driven rearrangement of biological cells. Phys. Rev. E 47, 2128–2154 (1993).

    Article  CAS  Google Scholar 

  39. 39

    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).

    Article  Google Scholar 

  40. 40

    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).

    Article  CAS  Google Scholar 

  41. 41

    Yang, X., Manning, M. L. & Marchetti, M. C. Aggregation and segregation of confined active particles. Soft Matter 10, 6477–6484 (2014).

    Article  CAS  Google Scholar 

  42. 42

    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).

    Article  Google Scholar 

  43. 43

    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).

    Article  CAS  Google Scholar 

  44. 44

    Szabo, A. et al. Collective cell motion in endothelial monolayers. Phys. Biol. 7, 046007 (2010).

    Article  CAS  Google Scholar 

  45. 45

    Kabla, A. J. Collective cell migration: Leadership, invasion and segregation. J. R. Soc. Interface 9, 3268–3278 (2012).

    Article  Google Scholar 

  46. 46

    Li, B. & Sun, S. X. Coherent motions in confluent cell monolayer sheets. Biophys. J. 107, 1532–1541 (2014).

    Article  CAS  Google Scholar 

  47. 47

    Attanasi, A. et al. Finite-size scaling as a way to probe near-criticality in natural swarms. Phys. Rev. Lett. 113, 238102 (2014).

    Article  CAS  Google Scholar 

  48. 48

    Fredberg, J. J. Power steering, power brakes, and jamming: Evolution of collective cell–cell interactions. Physiology 29, 218–219 (2014).

    Article  Google Scholar 

  49. 49

    Hidalgo, J. et al. Information-based fitness and the emergence of criticality in living systems. Proc. Natl Acad. Sci. USA 111, 10095–10100 (2014).

    Article  CAS  Google Scholar 

  50. 50

    Lazaar, A. L. & Panettieri, R. A. Jr Is airway remodeling clinically relevant in asthma? Am. J. Med. 115, 652–659 (2003).

    Article  Google Scholar 

  51. 51

    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).

    Article  CAS  Google Scholar 

  52. 52

    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).

    Article  CAS  Google Scholar 

  53. 53

    Trepat, X. et al. Universal physical responses to stretch in the living cell. Nature 447, 592–595 (2007).

    Article  CAS  Google Scholar 

  54. 54

    Serra-Picamal, X. et al. Mechanical waves during tissue expansion. Nature Phys. 8, 628–634 (2012).

    Article  CAS  Google Scholar 

  55. 55

    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).

    Article  CAS  Google Scholar 

  56. 56

    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).

    Article  CAS  Google Scholar 

  57. 57

    Efron, B. & Tibshirani, R. An Introduction to the Bootstrap (Chapman & Hall, 1993).

    Google Scholar 

Download references


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).

Author information




J.-A.P. designed experiments, carried out time-lapse imaging of HBECs in ALI culture and interpreted data. J.H.K. designed measurements of physical forces within HBECs and analysed data. J.H.K. and M.M. carried out force-measurement experiments. J.H.K., N.T.Q., C.Y.P. and C.H. analysed the dynamics of cellular motions. D.B. and J.A.M. analysed cell-shape parameters. D.B. modelled cell-shape parameters and cell motility. J.A.M. and S.-H.K. carried out time-lapse imaging of HBECs in ALI culture. D.T.T., B.G., J.N., R.S. and S.B. contributed to preparation of physical-force measurements. S.H.R. contributed to the design of experiments and provided primary HBECs. D.A.W., D.J.T., S.T.W., M.L.M., J.P.B., J.M.D. and J.J.F. guided data interpretation and analysis of cellular migration and the jamming transition. S.H.R., A.T.K., S.A.S., E.I., S.T.W., E.P.H., K.T. and J.M.D. guided data interpretation on the biological relevance of cellular migration. J.-A.P., J.H.K., D.B., M.L.M. and J.J.F., wrote the manuscript. J.-A.P. and J.J.F. oversaw the project.

Corresponding author

Correspondence to Jin-Ah Park.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 1953 kb)

Supplementary Information

Supplementary Movie 1 (MOV 7193 kb)

Supplementary Information

Supplementary Movie 2 (MOV 8065 kb)

Supplementary Information

Supplementary Movie 3 (MOV 12679 kb)

Supplementary Information

Supplementary Movie 4 (MOV 31176 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

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).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing