Solid stress and tissue stiffness affect tumour growth, invasion, metastasis and treatment. Unlike stiffness, which can be precisely mapped in tumours, the measurement of solid stresses is challenging. Here, we show that 2D spatial maps of the solid stress and the resulting elastic energy in excised or in situ tumours with arbitrary shapes and a wide range of sizes can be obtained via three distinct and quantitative techniques that rely on the measurement of tissue displacement after disruption of the confining structures. Application of these methods in models of primary tumours and metastasis revealed that (i) solid stress depends on both cancer cells and their microenvironments, (ii) solid stress increases with tumour size and (iii) mechanical confinement by the surrounding tissue substantially contributes to intratumoral solid stress. Further study of the genesis and consequences of solid stress, facilitated by the engineering principles presented here, may lead to new discoveries and therapies.

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We thank S. Roberge, C. Smith, J. Kahn and M. Duquette for technical assistance. We also thank P. Huang, N. Bardeesy and T. Irimura for providing MMTV-M3C, AK4.4 and SL4 cells, respectively. This work was supported in part by funding from the National Cancer Institute (P01-CA080124), an NCI Outstanding Investigator Award (R35-CA197743) and a Department of Defense Breast Cancer Research Innovator award (W81XWH-10-1-0016) to R.K.J., a DP2 OD008780 to T.P.P., a R01 grant (HL128168) to L.L.M., T.P.P. and J.W.B., a Susan G. Komen Foundation Fellowship (PDF14301739) to G.S., a National Institutes of Health award (F31HL126449) to M.D., and an UNCF-Merck Science Initiative Postdoctoral Fellowship, Burroughs Wellcome Fund Postdoctoral Enrichment Program Award and a NCI grant (F32CA183465) to D.J.

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  1. Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA

    • Hadi T. Nia
    • , Hao Liu
    • , Giorgio Seano
    • , Meenal Datta
    • , Dennis Jones
    • , Nuh Rahbari
    • , Joao Incio
    • , Vikash P. Chauhan
    • , Keehoon Jung
    • , John D. Martin
    • , Vasileios Askoxylakis
    • , Timothy P. Padera
    • , Dai Fukumura
    • , Yves Boucher
    • , Lance L. Munn
    •  & Rakesh K. Jain
  2. Leder Human Biology and Translational Medicine, Biology and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts 02115, USA

    • Hao Liu
  3. Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts 02155, USA

    • Meenal Datta
  4. Department of Internal Medicine, Hospital S. Joao, I3S, Institute for Innovation and Research in Health, and Faculty of Medicine, Porto University, 4200-319 Porto, Portugal

    • Joao Incio
  5. Orthopedic Oncology Service, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA

    • Francis J. Hornicek
  6. Center for Biomedical Engineering, Departments of Mechanical, Electrical and Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Alan J. Grodzinsky
  7. Department of Biomedical Engineering, Bucknell University, Lewisburg, Pennsylvania 17837, USA

    • James W. Baish


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H.T.N. and R.K.J. designed the study; H.T.N., H.L., G.S., M.D., D.J., N.R., J.I., K.J. performed the research; H.T.N., H.L., G.S., M.D., D.J., N.R., J.I., V.P.C., K.J., J.D.M., V.A., T.P.P., D.F., Y.B., F.J.H., A.J.G., J.W.B., L.L.M. and R.K.J. analysed the data; H.T.N., M.D., G.S., V.P.C., L.L.M. and R.K.J. wrote the manuscript.

Competing interests

R.K.J. received consultant fees from Ophthotech, SPARC, SynDevRx and XTuit. R.K.J. owns equity in Enlight, Ophthotech, SynDevRx and XTuit, and serves on the Board of Directors of XTuit and the Boards of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, the Tekla Healthcare Opportunities Fund and the Tekla World Healthcare Fund. No reagents or funding from these companies were used in these studies.

Corresponding author

Correspondence to Rakesh K. Jain.

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