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Unjamming and cell shape in the asthmatic airway epithelium

Nature Materials volume 14, pages 1040–1048 (2015)Cite this article

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Abstract

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.

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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.

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Acknowledgements

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).

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  1. Jin-Ah Park and Jae Hun Kim: These authors contributed equally to this work.

Authors and Affiliations

  1. Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA

    Jin-Ah Park, Jae Hun Kim, Jennifer A. Mitchel, Nader Taheri Qazvini, Chan Young Park, Maureen McGill, Sae-Hoon Kim, Bomi Gweon, Jacob Notbohm, Robert Steward Jr, Stephanie Burger, Dhananjay T. Tambe, Corey Hardin, Stephanie A. Shore, James P. Butler, Jeffrey M. Drazen & Jeffrey J. Fredberg

  2. Syracuse University, Syracuse, New York 13244, USA

    Dapeng Bi & M. Lisa Manning

  3. School of Chemistry, College of Science, University of Tehran, Tehran 14179, Iran

    Nader Taheri Qazvini

  4. Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA

    Kelan Tantisira, Elliot Israel, Elizabeth P. Henske, Scott T. Weiss & James P. Butler

  5. The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27514, USA

    Scott H. Randell

  6. Children’s Hospital, Boston, Massachusetts 02215, USA

    Alvin T. Kho

  7. Department of Mechanical Engineering, University of South Alabama, Mobile, Alabama 36688, USA

    Dhananjay T. Tambe

  8. Harvard University, Cambridge, Massachusetts 02138, USA

    David A. Weitz

  9. Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA

    Daniel J. Tschumperlin

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Contributions

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.

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Correspondence to Jin-Ah Park.

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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

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