Abstract
The past 20 years have witnessed ever-growing evidence that the mechanical properties of biological tissues, from nanoscale to macroscale dimensions, are fundamental for cellular behaviour and consequent tissue functionality. This knowledge, combined with previously known biochemical cues, has greatly advanced the field of biomaterial development, tissue engineering and regenerative medicine. It is now established that approaches to engineer biological tissues must integrate and approximate the mechanics, both static and dynamic, of native tissues. Nevertheless, the literature on the mechanical properties of biological tissues differs greatly in methodology, and the available data are widely dispersed. This Review gathers together the most important data on the stiffness of living tissues and discusses the intricacies of tissue stiffness from a materials perspective, highlighting the main challenges associated with engineering lifelike tissues and proposing a unified view of this as yet unreported topic. Emerging advances that might pave the way for the next decade’s take on bioengineered tissue stiffness are also presented, and differences and similarities between tissues in health and disease are discussed, along with various techniques for characterizing tissue stiffness at various dimensions from individual cells to organs.
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References
Callister, W. D. Jr & Rethwisch, D. G. Materials Science and Engineering: An Introduction 8th edn (Wiley, 2007).
Langer, R. & Vacanti, J. P. Tissue engineering. Science 260, 920–926 (1993).
Discher, D. E., Janmey, P. & Wang, Y. Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139–1143 (2005). A seminal work reporting for the first time that mechanics alone affect the behaviour of cells.
Yanez, L. Z., Han, J., Behr, B. B., Pera, R. A. R. & Camarillo, D. B. Human oocyte developmental potential is predicted by mechanical properties within hours after fertilization. Nat. Commun. 7, 10809 (2016).
Cross, S. E., Jin, Y. S., Rao, J. & Gimzewski, J. K. Nanomechanical analysis of cells from cancer patients. Nat. Nanotechnol. 2, 780–783 (2007).
Baumgart, F. & Cordey, J. Stiffness — an unknown world of mechanical science? Injury 32, 14–23 (2001).
Pang, Z., Deeth, H., Sopade, P., Sharma, R. & Bansal, N. Rheology, texture and microstructure of gelatin gels with and without milk proteins. Food Hydrocoll. 35, 484–493 (2014).
Koga, Y., Koga, T., Kinekawa, Y. & Kitabatake, N. Properties of a thermostable emulsion prepared from process whey protein and olive oil; use as a cream-substitute and its practical application to panna-cotta. J. Cook. Sci. Jpn 34, 154–163 (2001).
Williams, S. H., Wright, B. W., Truong, V., den, Daubert, C. R. & Vinyard, C. J. Mechanical properties of foods used in experimental studies of primate masticatory function. Am. J. Primatol. 67, 329–346 (2005).
Perry, J. M. G., Bastian, M. L., St Clair, E. & Hartstone-Rose, A. Maximum ingested food size in captive anthropoids. Am. J. Phys. Anthropol. 158, 92–104 (2015).
Davis, J. R. (ed.) Tensile Testing 2nd edn (ASM International, 2004).
Wong, B. L., Bae, W. C., Gratz, K. R. & Sah, R. L. Shear deformation kinematics during cartilage articulation: effect of lubrication, degeneration, and stress relaxation. Mol. Cell. Biomech. 5, 197–206 (2008).
Pothan, L. A., Oommen, Z. & Thomas, S. Dynamic mechanical analysis of banana fiber reinforced polyester composites. Compos. Sci. Technol. 63, 283–293 (2003).
Meyers, M. A. & Chawla, K. K. Mechanical Behavior of Materials 2nd edn (Cambridge Univ. Press, 2009).
Cross, R. Elastic and viscous properties of Silly Putty. Am. J. Phys. 80, 870–875 (2012).
Omari, E. A., Varghese, T., Kliewer, M. A., Harter, J. & Hartenbach, E. M. Dynamic and quasi-static mechanical testing for characterization of the viscoelastic properties of human uterine tissue. J. Biomech. 48, 1730–1736 (2015).
Karunaratne, A., Li, S. & Bull, A. M. J. Nano-scale mechanisms explain the stiffening and strengthening of ligament tissue with increasing strain rate. Sci. Rep. 8, 3707 (2018).
Wang, L. & Liu, X. Characterization of viscoelastic materials by quasi-static and dynamic indentation. Meas. Sci. Technol. 25, 064017 (2014).
Schapery, R. A. Two simple approximate methods of Laplace transform inversion for viscoelastic stress analysis. Calif. Inst. Technol. https://resolver.caltech.edu/CaltechAUTHORS:20141114-114344034 (1961).
Schapery, R. A. Stress analysis of viscoelastic composite materials. J. Compos. Mater. 1, 228–267 (1967).
Yofe, A. D. Physics at surfaces. Contemp. Phys. 29, 411–414 (1988).
Abazari, A. M., Safavi, S. M., Rezazadeh, G. & Villanueva, L. G. Modelling the size effects on the mechanical properties of micro/nano structures. Sensors 15, 28543–28562 (2015).
McNamara, L. E. et al. The role of microtopography in cellular mechanotransduction. Biomaterials 33, 2835–2847 (2012).
Peric, D. et al. On micro-to-macro transitions for multi-scale analysis of non-linear heterogeneous materials: unified variational basis and finite element implementation. Int. J. Numer. Methods Eng. 87, 149–170 (2011).
Geers, M. G. D., Kouznetsova, V. G. & Brekelmans, W. A. M. Multi-scale computational homogenization: trends and challenges. J. Comput. Appl. Math. 234, 2175–2182 (2010).
Speirs, D. C. D., de Souza Neto, E. A. & Perić, D. An approach to the mechanical constitutive modelling of arterial tissue based on homogenization and optimization. J. Biomech. 41, 2673–2680 (2008).
Hollister, S. J. & Lin, C. Y. Computational design of tissue engineering scaffolds. Comput. Methods Appl. Mech. Eng. 196, 2991–2998 (2007).
Kim, S. H., Turnbull, J. & Guimond, S. Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J. Endocrinol. 209, 139–151 (2011).
Miller, C. J. & Davidson, L. A. The interplay between cell signalling and mechanics in developmental processes. Nat. Rev. Genet. 14, 733–744 (2013).
Alcaraz, J. et al. Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia. EMBO J. 27, 2829–2838 (2008).
Keane, T. J., Horejs, C. M. & Stevens, M. M. Scarring vs. functional healing: matrix-based strategies to regulate tissue repair. Adv. Drug Deliv. Rev. 129, 407–419 (2018).
Sasaki, N. & Odajima, S. Stress–strain curve and Young’s modulus of a collagen molecule as determined by the X-ray diffraction technique. J. Biomech. 29, 655–658 (1996).
Wenger, M. P. E., Bozec, L., Horton, M. A. & Mesquidaz, P. Mechanical properties of collagen fibrils. Biophys. J. 93, 1255–1263 (2007).
Bornstein, P. & Sage, H. Structurally distinct collagen types. Annu. Rev. Biochem. 49, 957–1003 (1980).
Shoulders, M. D. & Raines, R. T. Collagen structure and stability. Annu. Rev. Biochem. 78, 929–958 (2009).
Zhang, W., Huang, Z. L., Liao, S. S. & Cui, F. Z. Nucleation sites of calcium phosphate crystals during collagen mineralization. J. Am. Ceram. Soc. 86, 1052–1054 (2003).
Herchenhan, A. et al. Tenocyte contraction induces crimp formation in tendon-like tissue. Biomech. Model. Mechanobiol. 11, 449–459 (2012).
Hornsby, J. et al. Quantitative multiphoton microscopy of murine urinary bladder morphology during in situ uniaxial loading. Acta Biomater. 64, 59–66 (2017).
Wiesinger, H. P., Rieder, F., Kösters, A., Müller, E. & Seynnes, O. R. Are sport-specific profiles of tendon stiffness and cross-sectional area determined by structural or functional integrity? PLoS One 11, e0158441 (2016).
Ma, Y., Feng, X., Rogers, J. A., Huang, Y. & Zhang, Y. Design and application of ‘J-shaped’ stress–strain behavior in stretchable electronics: a review. Lab. Chip 17, 1689–1704 (2017).
Wagenseil, J. E. & Mecham, R. P. Elastin in large artery stiffness and hypertension. J. Cardiovasc. Transl. Res. 5, 264–273 (2012).
Muiznieks, L. D., Weiss, A. S. & Keeley, F. W. Structural disorder and dynamics of elastin. Biochem. Cell Biol. 88, 239–250 (2010).
Muiznieks, L. D. & Keeley, F. W. Molecular assembly and mechanical properties of the extracellular matrix: a fibrous protein perspective. Biochim. Biophys. Acta 1832, 866–875 (2013).
Ryan, A. J. & O’Brien, F. J. Insoluble elastin reduces collagen scaffold stiffness, improves viscoelastic properties, and induces a contractile phenotype in smooth muscle cells. Biomaterials 73, 296–307 (2015).
Tsamis, A., Krawiec, J. T. & Vorp, D. A. Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review. J. R. Soc. Interface 10, 20121004 (2013).
Ahmadzadeh, H., Connizzo, B. K., Freedman, B. R., Soslowsky, L. J. & Shenoy, V. B. Determining the contribution of glycosaminoglycans to tendon mechanical properties with a modified shear-lag model. J. Biomech. 46, 2497–2503 (2013).
Quinn, T. M., Dierickx, P. & Grodzinsky, A. J. Glycosaminoglycan network geometry may contribute to anisotropic hydraulic permeability in cartilage under compression. J. Biomech. 34, 1483–1490 (2001).
Tavakoli Nia, H. et al. Aggrecan nanoscale solid–fluid interactions are a primary determinant of cartilage dynamic mechanical properties. ACS Nano 9, 2614–2625 (2015).
Klotzsch, E. et al. Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites. Proc. Natl Acad. Sci. USA 106, 18267–18272 (2009).
Dray, N. et al. Cell–fibronectin interactions propel vertebrate trunk elongation via tissue mechanics. Curr. Biol. 23, 1335–1341 (2013).
Gautieri, A., Uzel, S., Vesentini, S., Redaelli, A. & Buehler, M. J. Molecular and mesoscale mechanisms of osteogenesis imperfecta disease in collagen fibrils. Biophys. J. 97, 857–865 (2009).
Mavilio, F. et al. Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat. Med. 12, 1397–1402 (2006).
Wagner, J. E. et al. Bone marrow transplantation for recessive dystrophic epidermolysis bullosa. N. Engl. J. Med. 363, 629–639 (2010).
Germain, D. P. Clinical and genetic features of vascular Ehlers–Danlos syndrome. Ann. Vasc. Surg. 16, 391–397 (2002).
De Paepe, A. & Malfait, F. The Ehlers–Danlos syndrome, a disorder with many faces. Clin. Genet. 82, 1–11 (2012).
Von Erlach, T. C. et al. Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate. Nat. Mater. 17, 237–242 (2018).
Kasza, K. E. et al. The cell as a material. Curr. Opin. Cell Biol. 19, 101–107 (2007). This is the first article to consider cells as a material.
Suresh, S. Biomechanics and biophysics of cancer cells. Acta Mater. 55, 3989–4014 (2007).
Fletcher, D. A. & Mullins, R. D. Cell mechanics and the cytoskeleton. Nature 463, 485–492 (2010).
Kumar, S. et al. Viscoelastic retraction of single living stress fibers and its impact on cell shape, cytoskeletal organization, and extracellular matrix mechanics. Biophys. J. 90, 3762–3773 (2006).
Salbreux, G., Charras, G. & Paluch, E. Actin cortex mechanics and cellular morphogenesis. Trends Cell Biol. 22, 536–545 (2012). This article offers an interesting perspective on cell cortex dynamics.
Ingber, D. E. Tensegrity-based mechanosensing from macro to micro. Prog. Biophys. Mol. Biol. 97, 163–179 (2008). This article provides a complete overview of tensegrity in cell mechanics and its parallel with tensegrity architecture.
Ingber, D. E. From mechanobiology to developmentally inspired engineering. Phil. Trans. R. Soc. Lond. B Biol. Sci. 373, 20170323 (2018).
Mandriota, N. et al. Cellular nanoscale stiffness patterns governed by intracellular forces. Nat. Mater. 18, 1071–1077 (2019). The data in this article provide evidence of how much influence intracellular forces and states have on local cellular stiffness.
Condeelis, J. Life at the leading edge: the formation of cell protrusions. Annu. Rev. Cell Biol. 9, 411–444 (1993).
Charras, G. T., Yarrow, J. C., Horton, M. A., Mahadevan, L. & Mitchison, T. J. Non-equilibration of hydrostatic pressure in blebbing cells. Nature 435, 365–369 (2005).
Prost, J., Jülicher, F. & Joanny, J. F. Active gel physics. Nat. Phys. 11, 111–117 (2015). An article providing a complete description of the physics of active gels.
Guo, M. et al. Cell volume change through water efflux impacts cell stiffness and stem cell fate. Proc. Natl Acad. Sci. USA 114, E8618–E8627 (2017).
Lekka, M. & Laidler, P. Applicability of AFM in cancer detection. Nat. Nanotechnol. 4, 72–72 (2009).
Gavara, N. & Chadwick, R. S. Determination of the elastic moduli of thin samples and adherent cells using conical atomic force microscope tips. Nat. Nanotechnol. 7, 733–736 (2012).
Dimitriadis, E. K., Horkay, F., Maresca, J., Kachar, B. & Chadwick, R. S. Determination of elastic moduli of thin layers of soft material using the atomic force microscope. Biophys. J. 82, 2798–2810 (2002).
Rianna, C. & Radmacher, M. Comparison of viscoelastic properties of cancer and normal thyroid cells on different stiffness substrates. Eur. Biophys. J. 46, 309–324 (2017).
Kaushik, G., Fuhrmann, A., Cammarato, A. & Engler, A. J. In situ mechanical analysis of myofibrillar perturbation and aging on soft, bilayered Drosophila myocardium. Biophys. J. 101, 2629–2637 (2011).
Tan, J. L. et al. Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc. Natl Acad. Sci. USA 100, 1484–1489 (2003).
Tee, S. Y., Fu, J., Chen, C. S. & Janmey, P. A. Cell shape and substrate rigidity both regulate cell stiffness. Biophys. J. 100, L25–L27 (2011).
Gonzalez-Cruz, R. D., Fonseca, V. C. & Darling, E. M. Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells. Proc. Natl Acad. Sci. USA 109, E1523–E1529 (2012).
Yu, H. et al. Mechanical behavior of human mesenchymal stem cells during adipogenic and osteogenic differentiation. Biochem. Biophys. Res. Commun. 393, 150–155 (2010).
Norcross, S., Horsley, V., Mertz, A. F., Rosowski, K. A. & Dufresne, E. R. Edges of human embryonic stem cell colonies display distinct mechanical properties and differentiation potential. Sci. Rep. 5, 14218 (2015).
Poh, Y.-C. et al. Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells. Nat. Mater. 9, 82–88 (2009).
Das, R. K., Gocheva, V., Hammink, R., Zouani, O. F. & Rowan, A. E. Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels. Nat. Mater. 15, 318–325 (2015).
Leong, K. W., Yim, E. K. F., Kulangara, K., Darling, E. M. & Guilak, F. Nanotopography-induced changes in focal adhesions, cytoskeletal organization, and mechanical properties of human mesenchymal stem cells. Biomaterials 31, 1299–1306 (2009).
Conte, V. et al. Control of cell–cell forces and collective cell dynamics by the intercellular adhesome. Nat. Cell Biol. 17, 409–420 (2015).
Latorre, E. et al. Active superelasticity in three-dimensional epithelia of controlled shape. Nature 563, 203–208 (2018).
Vincent, R. et al. Active tensile modulus of an epithelial monolayer. Phys. Rev. Lett. 115, 248103 (2015).
Charras, G. & Yap, A. S. Tensile forces and mechanotransduction at cell–cell junctions. Curr. Biol. 28, R445–R457 (2018).
Khalilgharibi, N. et al. Stress relaxation in epithelial monolayers is controlled by the actomyosin cortex. Nat. Phys. 15, 839–847 (2019).
Gonzalez-Rodriguez, D., Guevorkian, K., Douezan, S. & Brochard-Wyart, F. Soft matter models of developing tissues and tumors. Science 338, 910–917 (2012).
Serwane, F. et al. In vivo quantification of spatially varying mechanical properties in developing tissues. Nat. Methods 14, 181–186 (2017).
Mongera, A. et al. A fluid-to-solid jamming transition underlies vertebrate body axis elongation. Nature 561, 401–405 (2018).
Stooke-Vaughan, G. A. & Campàs, O. Physical control of tissue morphogenesis across scales. Curr. Opin. Genet. Dev. 51, 111–119 (2018).
Rho, J. Y., Ashman, R. B. & Turner, C. H. Young’s modulus of trabecular and cortical bone material: ultrasonic and microtensile measurements. J. Biomech. 26, 111–119 (1993).
McDonald, S. J. et al. Early fracture callus displays smooth muscle-like viscoelastic properties ex vivo: implications for fracture healing. J. Orthop. Res. 27, 1508–1513 (2009).
Chaudhuri, O. et al. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat. Mater. 15, 326–334 (2015). A seminal work on the effect of controlled 3D stress relaxation on the behaviour of stem cells.
Chlasta, J. et al. Variations in basement membrane mechanics are linked to epithelial morphogenesis. Development 144, 4350–4362 (2017).
Vuong-Brender, T. T. K., Suman, S. K. & Labouesse, M. The apical ECM preserves embryonic integrity and distributes mechanical stress during morphogenesis. Development 144, 4336–4349 (2017).
Nerurkar, N. L., Lee, C. H., Mahadevan, L. & Tabin, C. J. Molecular control of macroscopic forces drives formation of the vertebrate hindgut. Nature 565, 480–484 (2019).
Benech, J. C. et al. Diabetes increases stiffness of live cardiomyocytes measured by atomic force microscopy nanoindentation. Am. J. Physiol. Physiol. 307, C910–C919 (2014).
Somlyo, A. P. et al. Ultrastructure, function and composition of smooth muscle. Ann. Biomed. Eng. 11, 579–588 (1983).
Darling, E. M., Topel, M., Zauscher, S., Vail, T. P. & Guilak, F. Viscoelastic properties of human mesenchymally-derived stem cells and primary osteoblasts, chondrocytes, and adipocytes. J. Biomech. 41, 454–464 (2008).
Li, X., Das, A. & Bi, D. Mechanical heterogeneity in tissues promotes rigidity and controls cellular invasion. Phys. Rev. Lett. 123, 058101 (2019).
Roduit, C. et al. Elastic membrane heterogeneity of living cells revealed by stiff nanoscale membrane domains. Biophys. J. 94, 1521–1532 (2008).
Marturano, J. E. et al. Embryonically inspired scaffolds regulate tenogenically differentiating cells. J. Biomech. 49, 3281–3288 (2016).
Sotres, J., Jankovskaja, S., Wannerberger, K. & Arnebrant, T. Ex-vivo force spectroscopy of intestinal mucosa reveals the mechanical properties of mucus blankets. Sci. Rep. 7, 1–14 (2017).
Tyler, W. J. The mechanobiology of brain function. Nat. Rev. Neurosci. 13, 867–878 (2012).
McKee, C. T., Last, J. A., Russell, P. & Murphy, C. J. Indentation versus tensile measurements of Young’s modulus for soft biological tissues. Tissue Eng. Part B Rev. 17, 155–164 (2011).
Does, M. D. et al. Insights into reference point indentation involving human cortical bone: Sensitivity to tissue anisotropy and mechanical behavior. J. Mech. Behav. Biomed. Mater. 37, 174–185 (2014).
Haase, K. & Pelling, A. Investigating cell mechanics with atomic force microscopy. J. R. Soc. Interface 12, 20140970 (2015).
Saxena, T., Gilbert, J., Stelzner, D. & Hasenwinkel, J. Mechanical characterization of the injured spinal cord after lateral spinal hemisection injury in the rat. J. Neurotrauma 29, 1747–1757 (2012).
Oakland, R. J., Hall, R. M., Wilcox, R. K. & Barton, D. C. The biomechanical response of spinal cord tissue to uniaxial loading. Proc. Inst. Mech. Eng. Part H 220, 489–492 (2006).
Pailler-Mattei, C., Bec, S. & Zahouani, H. In vivo measurements of the elastic mechanical properties of human skin by indentation tests. Med. Eng. Phys. 30, 599–606 (2008).
Pissarenko, A. et al. Tensile behavior and structural characterization of pig dermis. Acta Biomater. 86, 77–95 (2019).
Iskratsch, T., Wolfenson, H. & Sheetz, M. P. Appreciating force and shape — the rise of mechanotransduction in cell biology. Nat. Rev. Mol. Cell Biol. 15, 825–833 (2014).
Guo, K. & Buehler, M. J. Nature’s way: hierarchical strength weakness. Matter 1, 302–303 (2019).
Ramakrishna, S., Mayer, J., Wintermantel, E. & Leong, K. W. Biomedical applications of polymer-composite materials: a review. Compos. Sci. Technol. 61, 1189–1224 (2001).
Zhang, G. et al. Development of tendon structure and function: regulation of collagen fibrillogenesis. J. Musculoskelet. Neuronal Interact. 5, 5–21 (2005).
Agache, P. G., Monneur, C., Leveque, J. L. & De Rigal, J. Mechanical properties and Young’s modulus of human skin in vivo. Arch. Dermatol. Res. 269, 221–232 (1980).
Menon, G. K. New insights into skin structure: scratching the surface. Adv. Drug Deliv. Rev. 54, S3–S17 (2002).
Skulborstad, A. J., Swartz, S. M. & Goulbourne, N. C. Biaxial mechanical characterization of bat wing skin. Bioinspir. Biomim. 10, 36004 (2015).
Hamasaki, T., Yamaguchi, T. & Iwamoto, M. Estimating the influence of age-related changes in skin stiffness on tactile perception for static stimulations. J. Biomech. Sci. Eng. 13, 17–00575 (2018).
Cui, J., Lee, C. H., Delbos, A., McManus, J. J. & Crosby, A. J. Cavitation rheology of the eye lens. Soft Matter 7, 7827–7831 (2011).
Krag, S. & Andreassen, T. T. Mechanical properties of the human posterior lens capsule. Invest. Opthalmol. Vis. Sci. 44, 691 (2003).
Danielsen, C. C. Tensile mechanical and creep properties of Descemet’s membrane and lens capsule. Exp. Eye Res. 79, 343–350 (2004).
Besner, S., Scarcelli, G., Pineda, R. & Yun, S. H. In vivo Brillouin analysis of the aging crystalline lens. Invest. Ophthalmol. Vis. Sci. 57, 5093–5100 (2016).
Tenorio, L. E. M., Devine, K. J., Lee, J., Kowalewski, T. M. & Barocas, V. H. Biomechanics of human parietal pleura in uniaxial extension. J. Mech. Behav. Biomed. Mater. 75, 330–335 (2017).
Davis, N. F. et al. Urinary bladder vs gastrointestinal tissue: a comparative study of their biomechanical properties for urinary tract reconstruction. Urology 113, 235–240 (2018).
Faingold, A. et al. The effect of hydration on mechanical anisotropy, topography and fibril organization of the osteonal lamellae. J. Biomech. 47, 367–372 (2014).
Milovanovic, P. et al. Age-related deterioration in trabecular bone mechanical properties at material level: nanoindentation study of the femoral neck in women by using AFM. Exp. Gerontol. 47, 154–159 (2012).
Melo, E. et al. Effects of the decellularization method on the local stiffness of acellular lungs. Tissue Eng. Part C 20, 412–422 (2014).
Peloso, A. et al. The human pancreas as a source of protolerogenic extracellular matrix scaffold for a new-generation bioartificial endocrine pancreas. Ann. Surg. 264, 169–179 (2016).
Omidi, E. et al. Characterization and assessment of hyperelastic and elastic properties of decellularized human adipose tissues. J. Biomech. 47, 3657–3663 (2014).
Ocal, S., Ozcan, U. M., Basdogan, I. & Basdogan, C. Effect of preservation period on the viscoelastic material properties of soft tissues with implications for liver transplantation. J. Biomech. Eng. 132, 101007 (2010).
Yamashita, J., Furman, B. R., Rawls, H. R., Wang, X. & Agrawal, C. M. The use of dynamic mechanical analysis to assess the viscoelastic properties of human cortical bone. J. Biomed. Mater. Res. 58, 47–53 (2001).
Buckwalter, J. A. & Mankin, H. J. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instrum. Course Lect. 47, 487–504 (1998).
Zhu, W., Mow, V. C., Koob, T. J. & Eyre, D. R. Viscoelastic shear properties of articular cartilage and the effects of glycosidase treatments. J. Orthop. Res. 11, 771–781 (1993).
Nickien, M., Thambyah, A. & Broom, N. D. How a decreased fibrillar interconnectivity influences stiffness and swelling properties during early cartilage degeneration. J. Mech. Behav. Biomed. Mater. 75, 390–398 (2017).
Brommer, H. et al. Functional consequences of cartilage degeneration in the equine metacarpophalangeal joint: quantitative assessment of cartilage stiffness. Equine Vet. J. 37, 462–467 (2005).
Kamiya, A. & Togawa, T. Adaptive regulation of wall shear stress to flow change in the canine carotid artery. Am. J. Physiol. 239, H14–H21 (1980).
Alkhouli, N. et al. The mechanical properties of human adipose tissues and their relationships to the structure and composition of the extracellular matrix. AJP Endocrinol. Metab. 305, E1427–E1435 (2013).
Wood, L. K. & Brooks, S. V. Ten weeks of treadmill running decreases stiffness and increases collagen turnover in tendons of old mice. J. Orthop. Res. 34, 346–353 (2016).
Peñuela, L. et al. Atomic force microscopy for biomechanical and structural analysis of human dermis: a complementary tool for medical diagnosis and therapy monitoring. Exp. Dermatol. 27, 150–155 (2018).
Crichton, M. L. et al. The viscoelastic, hyperelastic and scale dependent behaviour of freshly excised individual skin layers. Biomaterials 32, 4670–4681 (2011).
Lampi, M. C. & Reinhart-King, C. A. Targeting extracellular matrix stiffness to attenuate disease: from molecular mechanisms to clinical trials. Sci. Transl Med. 10, eaao0475 (2018).
Stefanescu, H. et al. Spleen stiffness measurement using fibroscan for the noninvasive assessment of esophageal varices in liver cirrhosis patients. J. Gastroenterol. Hepatol. 26, 164–170 (2011).
Hu, X. et al. Indirect prediction of liver fibrosis by quantitative measurement of spleen stiffness using the fibroscan system. J. Ultrasound Med. 33, 73–81 (2014).
Veiga, Z. S. T. et al. Transient elastography evaluation of hepatic and spleen stiffness in patients with hepatosplenic schistosomiasis. Eur. J. Gastroenterol. Hepatol. 29, 730–735 (2017).
Pawluś, A. et al. Shear wave elastography of the spleen: evaluation of spleen stiffness in healthy volunteers. Abdom. Radiol. 41, 2169–2174 (2016).
Chien, C. H. et al. Transient elastography for spleen stiffness measurement in patients with cirrhosis role in degree of thrombocytopenia. J. Ultrasound Med. 35, 1849–1857 (2016).
Kalli, M. & Stylianopoulos, T. Defining the role of solid stress and matrix stiffness in cancer cell proliferation and metastasis. Front. Oncol. 8, 55 (2018).
Mancini, M. L. & Sonis, S. T. Mechanisms of cellular fibrosis associated with cancer regimen-related toxicities. Front. Pharmacol. 5, 51 (2014).
Coelho, N. M. & McCulloch, C. A. Contribution of collagen adhesion receptors to tissue fibrosis. Cell Tissue Res. 365, 521–538 (2016).
Martinez, F. J. et al. Idiopathic pulmonary fibrosis review. Nat. Rev. Dis. Prim. 3, 17074 (2017).
Meng, X. M., Nikolic-Paterson, D. J. & Lan, H. Y. Inflammatory processes in renal fibrosis. Nat. Rev. Nephrol. 10, 493–503 (2014).
Tsochatzis, E. A., Bosch, J. & Burroughs, A. K. Liver cirrhosis. Lancet 383, 1749–1761 (2014).
Li, Q., Chen, L. & Zhou, Y. Diagnostic accuracy of liver stiffness measurement in chronic hepatitis B patients with normal or mildly elevated alanine transaminase levels. Sci. Rep. 8, 5224 (2018).
Ogawa, S. et al. Relationship between liver tissue stiffness and histopathological findings analyzed by shear wave elastography and compression testing in rats with non-alcoholic steatohepatitis. J. Med. Ultrason. 43, 355–360 (2016).
Pang, J. X. Q. et al. Liver stiffness by transient elastography predicts liver-related complications and mortality in patients with chronic liver disease. PLoS One 9, e95776 (2014).
Desai, S. S. et al. Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha. Hepatology 64, 261–275 (2016).
Li, Q. S., Lee, G. Y. H., Ong, C. N. & Lim, C. T. AFM indentation study of breast cancer cells. Biochem. Biophys. Res. Commun. 374, 609–613 (2008).
Gaikwad, R. M., Woodworth, C. D., Sokolov, I., Subba-Rao, V. & Iyer, S. Atomic force microscopy detects differences in the surface brush of normal and cancerous cells. Nat. Nanotechnol. 4, 389–393 (2009).
Wong, R. et al. AFM-based analysis of human metastatic cancer cells. Nanotechnology 19, 384003 (2008).
Lekka, M. Discrimination between normal and cancerous cells using AFM. Bionanoscience 6, 65–80 (2016).
Maciaszek, J. L. & Lykotrafitis, G. Sickle cell trait human erythrocytes are significantly stiffer than normal. J. Biomech. 44, 657–661 (2011).
Lin, H.-H. et al. Mechanical phenotype of cancer cells: cell softening and loss of stiffness sensing. Oncotarget 6, 20946–20958 (2015).
Gilkes, D. M. et al. Hypoxia-inducible factors mediate coordinated RhoA-ROCK1 expression and signaling in breast cancer cells. Proc. Natl Acad. Sci. USA 111, E384–E393 (2014).
Dvorak, H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 315, 1650–1659 (1986).
Dias Carvalho, P. et al. KRAS oncogenic signaling extends beyond cancer cells to orchestrate the microenvironment. Cancer Res. 78, 7–14 (2018).
Huang, S. & Ingber, D. E. Cell tension, matrix mechanics, and cancer development. Cancer Cell 8, 175–176 (2005).
Lyshchik, A. et al. Elastic moduli of thyroid tissues under compression. Ultrason. Imaging 110, 101–110 (2005).
Murphy, M. C. et al. Regional brain stiffness changes across the Alzheimer’s disease spectrum. Neuroimage Clin. 10, 283–290 (2016).
Chaturvedi, R. R. et al. Passive stiffness of myocardium from congenital heart disease and implications for diastole. Circulation 121, 979–988 (2010).
Vardakastani, V. et al. Increased intra-cortical porosity reduces bone stiffness and strength in pediatric patients with osteogenesis imperfecta. Bone 69, 61–67 (2014).
Ye, K. et al. Matrix stiffness and nanoscale spatial organization of cell-adhesive ligands direct stem cell fate. Nano Lett. 15, 4720–4729 (2015).
Zhou, Q. et al. Development of a novel orthogonal double gradient for high-throughput screening of mesenchymal stem cells–materials interaction. Adv. Mater. Interfaces 5, 4–11 (2018).
Garreta, E. et al. Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells. Nat. Mater. 18, 397–405 (2019).
Uynuk-Ool, T. et al. The geometrical shape of mesenchymal stromal cells measured by quantitative shape descriptors is determined by the stiffness of the biomaterial and by cyclic tensile forces. J. Tissue Eng. Regen. Med. 11, 3508–3522 (2017).
Branco da Cunha, C. et al. Influence of the stiffness of three-dimensional alginate/collagen-I interpenetrating networks on fibroblast biology. Biomaterials 35, 8927–8936 (2014).
Xie, J. et al. Substrate elasticity regulates adipose-derived stromal cell differentiation towards osteogenesis and adipogenesis through β-catenin transduction. Acta Biomater. 79, 83–95 (2018).
Lv, H. et al. Biomaterial stiffness determines stem cell fate. Life Sci. 178, 42–48 (2017).
Sun, A. X. et al. Chondrogenesis of human bone marrow mesenchymal stem cells in 3-dimensional, photocrosslinked hydrogel constructs: Effect of cell seeding density and material stiffness. Acta Biomater. 58, 302–311 (2016).
Hadden, W. J. et al. Stem cell migration and mechanotransduction on linear stiffness gradient hydrogels. Proc. Natl Acad. Sci. USA 114, 5647–5652 (2017).
Xi, W., Saw, T. B., Delacour, D., Lim, C. T. & Ladoux, B. Material approaches to active tissue mechanics. Nat. Rev. Mater. 4, 23–44 (2019).
Chaudhuri, O. et al. Substrate stress relaxation regulates cell spreading. Nat. Commun. 19, 6364 (2015).
Guvendiren, M. & Burdick, J. A. Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics. Nat. Commun. 3, 792 (2012).
Storm, C., Pastore, J. J., MacKintosh, F. C., Lubensky, T. C. & Janmey, P. A. Nonlinear elasticity in biological gels. Nature 435, 191–194 (2005).
Kouwer, P. H. J. et al. Responsive biomimetic networks from polyisocyanopeptide hydrogels. Nature 493, 651–655 (2013).
de Almeida, P. et al. Cytoskeletal stiffening in synthetic hydrogels. Nat. Commun. 10, 609 (2019). A seminal work showing that hydrogels with cytoskeletal-like stress stiffening can be obtained.
Dhume, R. Y. & Barocas, V. H. Emergent structure-dependent relaxation spectra in viscoelastic fiber networks in extension. Acta Biomater. 87, 245–255 (2019).
Lee, H. P., Gu, L., Mooney, D. J., Levenston, M. E. & Chaudhuri, O. Mechanical confinement regulates cartilage matrix formation by chondrocytes. Nat. Mater. 16, 1243–1251 (2017).
Kim, B. S., Nikolovski, J., Bonadio, J. & Mooney, D. J. Cyclic mechanical strain regulates the development of engineered smooth muscle tissue. Nat. Biotechnol. 17, 979–983 (1999).
Cochis, A. et al. Bioreactor mechanically guided 3D mesenchymal stem cell chondrogenesis using a biocompatible novel thermo-reversible methylcellulose-based hydrogel. Sci. Rep. 7, 45018 (2017).
Chu, S.-Y. et al. Mechanical stretch induces hair regeneration through the alternative activation of macrophages. Nat. Commun. 10, 1524 (2019).
Lee, J. K. et al. Tension stimulation drives tissue formation in scaffold-free systems. Nat. Mater. 16, 864–873 (2017).
Tsimbouri, P. M. et al. Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor. Nat. Biomed. Eng. 1, 758–770 (2017).
Wisdom, K. M. et al. Matrix mechanical plasticity regulates cancer cell migration through confining microenvironments. Nat. Commun. 9, 4144 (2018).
Miotto, M. et al. 4D corneal tissue engineering: achieving time-dependent tissue self-curvature through localized control of cell actuators. Adv. Funct. Mater. 29, 1807334 (2019).
Loebel, C., Mauck, R. L. & Burdick, J. A. Local nascent protein deposition and remodelling guide mesenchymal stromal cell mechanosensing and fate in three-dimensional hydrogels. Nat. Mater. 18, 883–891 (2019). This article together with references 194 and 195 are important studies that serve as the foundation for our definition of biolabile environments and show the importance of allowing cells to ‘master their own fate’.
Qiao, E. L., Kumar, S. & Schaffer, D. V. Mastering their own fates through the matrix. Nat. Mater. 18, 779–780 (2019).
Vert, M., Li, S. M., Spenlehauer, G. & Guerin, P. Bioresorbability and biocompatibility of aliphatic polyesters. J. Mater. Sci. 3, 432–446 (1992).
Hutmacher, D. W. Scaffolds in tissue engineering bone and cartilage. Biomaterials 21, 2529–2543 (2000).
Deringer, V. L., Caro, M. A. & Csányi, G. Machine learning interatomic potentials as emerging tools for materials science. Adv. Mater. 31, 1902765 (2019).
Ansari, S., Khorshidi, S. & Karkhaneh, A. Engineering of gradient osteochondral tissue: from nature to lab. Acta Biomater. 87, 41–54 (2019).
Silva, E. D. et al. Multifunctional magnetic-responsive hydrogels to engineer tendon-to-bone interface. Nanomedicine 14, 2375–2385 (2018).
Calejo, I., Costa‐Almeida, R., Reis, R. L. & Gomes, M. E. A textile platform using continuous aligned and textured composite microfibers to engineer tendon‐to‐bone interface gradient scaffolds. Adv. Healthc. Mater. 8, 1900200 (2019).
Ribeiro, V. P. et al. Enzymatically cross-linked silk fibroin-based hierarchical scaffolds for osteochondral regeneration. ACS Appl. Mater. Interfaces 11, 3781–3799 (2019).
Canadas, R. F. et al. Biochemical gradients to generate 3D heterotypic-like tissues with isotropic and anisotropic architectures. Adv. Funct. Mater. 28, 1804148 (2018).
Calejo, I., Costa-Almeida, R., Reis, R. L. & Gomes, M. E. A physiology-inspired multifactorial toolbox in soft-to-hard musculoskeletal interface tissue engineering. Trends Biotechnol. 38, 83–98 (2019).
Grigoryan, B. et al. Multivascular networks and functional intravascular topologies within biocompatible hydrogels. Science 364, 458–464 (2019).
Chimene, D., Lennox, K. K., Kaunas, R. R. & Gaharwar, A. K. Advanced bioinks for 3D printing: a materials science perspective. Ann. Biomed. Eng. 44, 2090–2102 (2016).
Bertoldi, K., Vitelli, V., Christensen, J. & Van Hecke, M. Flexible mechanical metamaterials. Nat. Rev. Mater. 2, 17066 (2017).
Frenzel, T., Kadic, M. & Wegener, M. Three-dimensional mechanical metamaterials with a twist. Science 358, 1027–1032 (2017).
Zhao, Z., Fang, R., Rong, Q. & Liu, M. Bioinspired nanocomposite hydrogels with highly ordered structures. Adv. Mater. 29, 1703045 (2017).
Chen, T., Bakhshi, H., Liu, L., Ji, J. & Agarwal, S. Combining 3D printing with electrospinning for rapid response and enhanced designability of hydrogel actuators. Adv. Funct. Mater. 28, 1800514 (2018).
Ingber, D. E. Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton. J. Cell Sci. 104, 613–627 (1993).
Fabry, B. et al. Scaling the microrheology of living cells. Phys. Rev. Lett. 87, 148102 (2001).
Stamenović, D. et al. Rheological behavior of living cells is timescale-dependent. Biophys. J. 93, 39–41 (2007).
Ingber, D. E., Wang, N. & Stamenović, D. Tensegrity, cellular biophysics, and the mechanics of living systems. Rep. Prog. Phys. 77, 046603 (2014).
Yip, A. K. et al. Anisotropic traction stresses and focal adhesion polarization mediates topography-induced cell elongation. Biomaterials 181, 103–112 (2018).
Saruwatari, L. et al. Osteoblasts generate harder, stiffer, and more delamination-resistant mineralized tissue on titanium than on polystyrene, associated with distinct tissue micro- and ultrastructure. J. Bone Miner. Res. 20, 2002–2016 (2005).
Kalyan Phani, M., Kumar, A., Arnold, W. & Samwer, K. Elastic stiffness and damping measurements in titanium alloys using atomic force acoustic microscopy. J. Alloys Compd. 676, 397–406 (2016).
Brown, A. L. et al. 22 week assessment of bladder acellular matrix as a bladder augmentation material in a porcine model. Biomaterials 23, 2179–2190 (2002).
Barak, M. M. & Black, M. A. A novel use of 3D printing model demonstrates the effects of deteriorated trabecular bone structure on bone stiffness and strength. J. Mech. Behav. Biomed. Mater. 78, 455–464 (2018).
Ramadan, S., Paul, N. & Naguib, H. E. Standardized static and dynamic evaluation of myocardial tissue properties. Biomed. Mater. 12, 025013 (2017).
Yoo, L., Gupta, V., Lee, C., Kavehpore, P. & Demer, J. L. Viscoelastic properties of bovine orbital connective tissue and fat: constitutive models. Biomech. Model. Mechanobiol. 10, 901–914 (2012).
Schachar, R. A., Chan, R. W. & Fu, M. Viscoelastic properties of fresh human lenses under 40 years of age: implications for the aetiology of presbyopia. Br. J. Ophthalmol. 95, 1010–1013 (2011).
Ozawa, H., Matsumoto, T., Ohashi, T., Sato, M. & Kokubun, S. Comparison of spinal cord gray matter and white matter softness: measurement by pipette aspiration method. J. Neurosurg. Spine 95, 221–224 (2001).
Lee, L. M. & Liu, A. P. The application of micropipette aspiration in molecular mechanics of single cells. J. Nanotechnol. Eng. Med. 5, 040902 (2014).
Moshtagh, P. R., Pouran, B., Korthagen, N. M., Zadpoor, A. A. & Weinans, H. Guidelines for an optimized indentation protocol for measurement of cartilage stiffness: the effects of spatial variation and indentation parameters. J. Biomech. 49, 3602–3607 (2016).
Uriarte, J. J. et al. Early impairment of lung mechanics in a murine model of Marfan syndrome. PLoS One 11, e0152124 (2016).
Shi, Y., Glaser, K. J., Venkatesh, S. K., Ben-Abraham, E. I. & Ehman, R. L. Feasibility of using 3D MR elastography to determine pancreatic stiffness in healthy volunteers. J. Magn. Reson. Imaging 41, 369–375 (2015).
Murphy, M. C. et al. Measuring the characteristic topography of brain stiffness with magnetic resonance elastography. PLoS One 8, e81668 (2013).
Anvari, A., Dhyani, M., Stephen, A. E. & Samir, A. E. Reliability of shear-wave elastography estimates of the Young modulus of tissue in follicular thyroid neoplasms. Am. J. Roentgenol. 206, 609–616 (2016).
Dutov, P., Antipova, O., Varma, S., Orgel, J. P. R. O. & Schieber, J. D. Measurement of elastic modulus of collagen type I single fiber. PLoS One 11, e0145711 (2016).
Li, W. et al. Fibrin fiber stiffness is strongly affected by fiber diameter, but not by fibrinogen glycation. Biophys. J. 110, 1400–1410 (2016).
Collet, J.-P., Shuman, H., Ledger, R. E., Lee, S. & Weisel, J. W. The elasticity of an individual fibrin fiber in a clot. Proc. Natl Acad. Sci. USA 102, 9133–9137 (2005).
Aaron, B. B. & Gosline, J. M. Elastin as a random‐network elastomer: a mechanical and optical analysis of single elastin fibers. Biopolymers 20, 1247–1260 (1981).
Gosline, J. et al. Elastic proteins: biological roles and mechanical properties. Phil. Trans. R. Soc. Lond. B Biol. Sci. 357, 121–132 (2002).
Zahn, J. T. et al. Age-dependent changes in microscale stiffness and mechanoresponses of cells. Small 7, 1480–1487 (2011).
Alcaraz, J. et al. Microrheology of human lung epithelial cells measured by atomic force microscopy. Biophys. J. 84, 2071–2079 (2003).
Nakamura, K. et al. Altered nano/micro-order elasticity of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Int. J. Cardiol. 140, 102–107 (2010).
Lulevich, V., Yang, H. Y., Isseroff, R. R. & Liu, G. Y. Single cell mechanics of keratinocyte cells. Ultramicroscopy 110, 1435–1442 (2010).
Siamantouras, E., Hills, C. E., Squires, P. E. & Liu, K. K. Quantifying cellular mechanics and adhesion in renal tubular injury using single cell force spectroscopy. Nanomedicine 12, 1013–1021 (2016).
Sun, S., Song, Z., Cotler, S. J. & Cho, M. Biomechanics and functionality of hepatocytes in liver cirrhosis. J. Biomech. 47, 2205–2210 (2014).
Hozic, A., Rico, F., Colom, A., Buzhynskyy, N. & Scheuring, S. Nanomechanical characterization of the stiffness of eye lens cells: a pilot study. Invest. Ophthalmol. Vis. Sci. 53, 2151–2156 (2012).
Kolipaka, A. et al. Magnetic resonance elastography to estimate brain stiffness: measurement reproducibility and its estimate in pseudotumor cerebri patients. Clin. Imaging 51, 114–122 (2018).
Arani, A. et al. Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults. Neuroimage 111, 59–64 (2015).
Ma, Z. et al. In vitro and in vivo mechanical properties of human ulnar and median nerves. J. Biomed. Mater. Res. A 101, 2718–2725 (2013).
Robinson, D. L. et al. Mechanical properties of normal and osteoarthritic human articular cartilage. J. Mech. Behav. Biomed. Mater. 61, 96–109 (2016).
Comley, K. & Fleck, N. A. A micromechanical model for the Young’s modulus of adipose tissue. Int. J. Solids Struct. 47, 2982–2990 (2010).
Savelberg, H. H. C. M., Kooloos, J. G. M., Huiskes, R. & Kauer, J. M. G. Stiffness of the ligaments of the human wrist joint. J. Biomech. 25, 369–376 (1992).
Przybylski, G. J., Carlin, G. J., Patel, P. R. & Woo, S. L. Y. Human anterior and posterior cervical longitudinal ligaments possess similar tensile properties. J. Orthop. Res. 14, 1005–1008 (1996).
Pintar, F. A. Geometric and mechanical properties of human cervical spine ligaments. J. Biomed. Eng. 122, 623–629 (2000).
Arani, A. et al. Cardiac MR elastography for quantitative assessment of elevated myocardial stiffness in cardiac amyloidosis. J. Magn. Reson. Imaging 46, 1361–1367 (2017).
Domian, I. J., Yu, H. & Mittal, N. On materials for cardiac tissue engineering. Adv. Healthc. Mater. 6, 1600768 (2017).
Eby, S. F. et al. Shear wave elastography of passive skeletal muscle stiffness: influences of sex and age throughout adulthood. Clin. Biomech. 30, 22–27 (2015).
Leong, H. T., Hug, F. & Fu, S. N. Increased upper trapezius muscle stiffness in overhead athletes with rotator cuff tendinopathy. PLoS One 11, e0155187 (2016).
Brandenburg, J. E. et al. Feasibility and reliability of quantifying passive muscle stiffness in young children by using shear wave ultrasound elastography. J. Ultrasound Med. 34, 663–670 (2015).
Souron, R. et al. Sex differences in active tibialis anterior stiffness evaluated using supersonic shear imaging. J. Biomech. 49, 3534–3537 (2016).
Wang, L., Yan, F., Yang, Y., Xiang, X. & Qiu, L. Quantitative assessment of skin stiffness in localized scleroderma using ultrasound shear-wave elastography. Ultrasound Med. Biol. 43, 1339–1347 (2017).
Marinelli, J. P. et al. Quantitative assessment of lung stiffness in patients with interstitial lung disease using MR elastography. J. Magn. Reson. Imaging 46, 365–374 (2017).
Mariappan, Y. K. et al. Estimation of the absolute shear stiffness of human lung parenchyma using 1 h spin echo, echo planar MR elastography. J. Magn. Reson. Imaging 40, 1230–1237 (2014).
Booth, A. J. et al. Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am. J. Respir. Crit. Care Med. 186, 866–876 (2012).
Bensamoun, S. F., Robert, L., Leclerc, G. E., Debernard, L. & Charleux, F. Stiffness imaging of the kidney and adjacent abdominal tissues measured simultaneously using magnetic resonance elastography. Clin. Imaging 35, 284–287 (2011).
Samir, A. E. et al. Shear wave elastography in chronic kidney disease: a pilot experience in native kidneys. BMC Nephrol. 16, 119 (2015).
Ling, W. et al. Effects of vascularity and differentiation of hepatocellular carcinoma on tumor and liver stiffness: in vivo and in vitro studies. Ultrasound Med. Biol. 40, 739–746 (2014).
Cha, S. W. et al. Nondiseased liver stiffness measured by shearwave elastography: a pilot study. J. Ultrasound Med. 33, 53–60 (2014).
Leal-Egaña, A. et al. Tuning liver stiffness against tumours: an in vitro study using entrapped cells in tumour-like microcapsules. J. Mech. Behav. Biomed. Mater. 9, 113–121 (2012).
Lee, D. H., Lee, J. M., Han, J. K. & Choi, B. I. MR elastography of healthy liver parenchyma: normal value and reliability of the liver stiffness value measurement. J. Magn. Reson. Imaging 38, 1215–1223 (2013).
Venkatesh, S. K., Wang, G., Teo, L. L. S. & Ang, B. W. L. Magnetic resonance elastography of liver in healthy Asians: normal liver stiffness quantification and reproducibility assessment. J. Magn. Reson. Imaging 39, 1–8 (2014).
Gangadhar, K., Hippe, D. S., Thiel, J. & Dighe, M. Impact of image orientation on measurements of thyroid nodule stiffness using shear wave elastography. J. Ultrasound Med. 35, 1661–1667 (2016).
Brezak, R., Hippe, D., Thiel, J. & Dighe, M. K. Variability in stiffness assessment in a thyroid nodule using shear wave imaging. Ultrasound Q. 31, 243–249 (2015).
Lam, A. C. L., Pang, S. W. A., Ahuja, A. T. & Bhatia, K. S. S. The influence of precompression on elasticity of thyroid nodules estimated by ultrasound shear wave elastography. Eur. Radiol. 26, 2845–2852 (2016).
Bahn, M. M. et al. Development and application of magnetic resonance elastography of the normal and pathological thyroid gland in vivo. J. Magn. Reson. Imaging 30, 1151–1154 (2009).
Pozzi, R. et al. Point shear-wave elastography in chronic pancreatitis: a promising tool for staging disease severity. Pancreatology 17, 905–910 (2017).
An, H., Shi, Y., Guo, Q. & Liu, Y. Test–retest reliability of 3D EPI MR elastography of the pancreas. Clin. Radiol. 71, 1068.e7–1068.e12 (2016).
Kolipaka, A. et al. Magnetic resonance elastography of the pancreas: measurement reproducibility and relationship with age. Magn. Reson. Imaging 42, 1–7 (2017).
Nenadic, I. et al. Noninvasive evaluation of bladder wall mechanical properties as a function of filling volume: potential application in bladder compliance assessment. PLoS One 11, e0157818 (2016).
Matalia, J. et al. Correlation of corneal biomechanical stiffness with refractive error and ocular biometry in a pediatric population. Cornea 36, 1221–1226 (2017).
Last, J. A., Thomasy, S. M., Croasdale, C. R., Russell, P. & Murphy, C. J. Compliance profile of the human cornea as measured by atomic force microscopy. Micron 43, 1293–1298 (2012).
Jardeleza, M. S. R., Daly, M. K., Kaufman, J. D., Klapperich, C. & Legutko, P. A. Effect of trypan blue staining on the elastic modulus of anterior lens capsules of diabetic and nondiabetic patients. J. Cataract Refract. Surg. 35, 318–323 (2009).
Acknowledgements
The authors gratefully acknowledge financial support from the European Research Council, grant agreement ERC-2012-ADG 20120216-321266 (project ComplexiTE). C.F.G. acknowledges scholarship grant no. PD/BD/135253/2017 from Fundação para a Ciência e Tecnologia. The authors also thank the peer-reviewers for their constructive comments and suggestions that helped to shape the manuscript.
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C.F.G. and L.G. contributed to all aspects of the article. R.L.R. and A.P.M. contributed substantially to discussions of the article content and review or editing of the manuscript before submission. A.P.M. additionally contributed to writing the manuscript.
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Guimarães, C.F., Gasperini, L., Marques, A.P. et al. The stiffness of living tissues and its implications for tissue engineering. Nat Rev Mater 5, 351–370 (2020). https://doi.org/10.1038/s41578-019-0169-1
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DOI: https://doi.org/10.1038/s41578-019-0169-1