Abstract
Cells display a high degree of functional organization, largely attributed to the intracellular biopolymer scaffold known as the cytoskeleton. This inherently complex structure drives the system out of equilibrium by constantly consuming energy to conserve or reorganize its structure. Thus, the active, structurally organized cytoskeleton is the key player for the emergent mechanical properties of cells, which further determine properties of cell clusters and even multicellular organisms. In this spirit, this chapter introduces the physical principles on the different levels of biological complexity ranging from single biopolymers to tissues. The emergent mechanical properties and their respective effects on each level will be highlighted with a strong emphasis on their intertwined nature.
Similar content being viewed by others
References
Anderson PW. More is different. Science. 1972;177(4047):393–6. https://doi.org/10.1126/science.177.4047.393.
Laughlin RB, Pines D. The theory of everything. Proc Natl Acad Sci U S A. 2000;97(1):28–31. https://doi.org/10.1073/pnas.97.1.28.
Schrödinger E. What is life?: the physical aspect of the living cell, Canto. Cambridge: Cambridge University Press; 2010.
Ryan AJ. Emergence is coupled to scope, not level. Complexity. 2007;13(2):67–77. https://doi.org/10.1002/cplx.20203.
Dawkins R The blind watchmaker: why the evidence of evolution reveals a universe without design. New edition [reissue] ed. New York: W. W. Norton; 1996.
Schuster P. A beginning of the end of the holism versus reductionism debate?: molecular biology goes cellular and organismic. Complexity. 2007;13(1):10–3. https://doi.org/10.1002/cplx.20193.
Huber F, Schnauss J, Ronicke S, et al. Emergent complexity of the cytoskeleton: from single filaments to tissue. Adv Phys. 2013;62(1):1–112. https://doi.org/10.1080/00018732.2013.771509.
Huber F, Kas J. Self-regulative organization of the cytoskeleton. Cytoskeleton. 2011;68(5):259–65. https://doi.org/10.1002/cm.20509.
Halley JD, Winkler DA. Classification of emergence and its relation to self-organization. Complexity. 2008;13(5):10–5. https://doi.org/10.1002/cplx.20216.
Halley JD, Winkler DA. Consistent concepts of self-organization and self-assembly. Complexity. 2008;14(2):10–7. https://doi.org/10.1002/cplx.20235.
Alberts B. Molecular biology of the cell: [MBOC]. 6th ed. New York: GS Garland Science; 2015.
Doi M, Edwards SF. The theory of polymer dynamics, The international series of monographs on physics, vol. 73. Oxford: Clarendon Press; 2003.
Schuldt C, Schnauß J, Händler T, et al. Tuning synthetic semiflexible networks by bending stiffness. Phys Rev Lett. 2016;117(19):197801. https://doi.org/10.1103/PhysRevLett.117.197801.
Isambert H, Venier P, Maggs A, et al. Flexibility of actin filaments derived from thermal fluctuations. Effect of bound nucleotide, phalloidin, and muscle regulatory proteins. J Biol Chem. 1995;270(19):11437–44. https://doi.org/10.1074/jbc.270.19.11437.
Isambert H, Maggs AC. Dynamics and rheology of actin solutions. Macromolecules. 1996;29(3):1036–40. https://doi.org/10.1021/ma946418x.
Greenberg MJ, Wang C-LA, Lehman W, et al. Modulation of actin mechanics by caldesmon and tropomyosin. Cell Motil Cytoskeleton. 2008;65(2):156–64. https://doi.org/10.1002/cm.20251.
Janson ME, Dogterom M. A bending mode analysis for growing microtubules: evidence for a velocity-dependent rigidity. Biophys J. 2004;87(4):2723–36. https://doi.org/10.1529/biophysj.103.038877.
Yin P, Hariadi RF, Sahu S, et al. Programming DNA tube circumferences. Science. 2008;321(5890):824–6. https://doi.org/10.1126/science.1157312.
Schiffels D, Liedl T, Fygenson DK. Nanoscale structure and microscale stiffness of DNA nanotubes. ACS Nano. 2013;7(8):6700–10. https://doi.org/10.1021/nn401362p.
Glaser M, Schnauß J, Tschirner T, et al. Self-assembly of hierarchically ordered structures in DNA nanotube systems. New J Phys. 2016;18(5):55001. https://doi.org/10.1088/1367-2630/18/5/055001.
Pollard TD, Blanchoin L, Mullins RD. Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. Annu Rev Biophys Biomol Struct. 2000;29:545–76. https://doi.org/10.1146/annurev.biophys.29.1.545.
Schnauß J, Händler T, Käs J. Semiflexible biopolymers in bundled arrangements. Polymers. 2016;8(8):274. https://doi.org/10.3390/polym8080274.
Schnauss J, Golde T, Schuldt C, et al. Transition from a linear to a harmonic potential in collective dynamics of a multifilament actin bundle. Phys Rev Lett. 2016;116(10):108102. https://doi.org/10.1103/PhysRevLett.116.108102.
Lansky Z, Braun M, Ludecke A, et al. Diffusible crosslinkers generate directed forces in microtubule networks. Cell. 2015;160(6):1159–68. https://doi.org/10.1016/j.cell.2015.01.051.
Braun M, Lansky Z, Hilitski F, et al. Entropic forces drive contraction of cytoskeletal networks. BioEssays. 2016;38(5):474–81. https://doi.org/10.1002/bies.201500183.
Ward A, Hilitski F, Schwenger W, et al. Solid friction between soft filaments. Nat Mater. 2015;14(6):583–8. https://doi.org/10.1038/nmat4222.
Hilitski F, Ward AR, Cajamarca L, et al. Measuring cohesion between macromolecular filaments one pair at a time: depletion-induced microtubule bundling. Phys Rev Lett. 2015;114(13):138102. https://doi.org/10.1103/PhysRevLett.114.138102.
Huber F, Strehle D, Schnauß J, et al. Formation of regularly spaced networks as a general feature of actin bundle condensation by entropic forces. New J Phys. 2015;17(4):43029. https://doi.org/10.1088/1367-2630/17/4/043029.
Daniel JL, Molish IR, Robkin L, et al. Nucleotide exchange between cytosolic ATP and F-actin-bound ADP may be a major energy-utilizing process in unstimulated platelets. Eur J Biochem. 1986;156(3):677–83. https://doi.org/10.1111/j.1432-1033.1986.tb09631.x.
Bernstein BW, Bamburg JR. Actin-ATP hydrolysis is a major energy drain for neurons. J Neurosci. 2003;23(1):1–6.
Block J, Schroeder V, Pawelzyk P, et al. Physical properties of cytoplasmic intermediate filaments. Biochim Biophys Acta. 2015;1853(11 Pt B):3053–64. https://doi.org/10.1016/j.bbamcr.2015.05.009.
Herrmann H, Bar H, Kreplak L, et al. Intermediate filaments: from cell architecture to nanomechanics. Nat Rev Mol Cell Biol. 2007;8(7):562–73. https://doi.org/10.1038/nrm2197.
Herrmann H, Aebi U. Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular scaffolds. Annu Rev Biochem. 2004;73:749–89. https://doi.org/10.1146/annurev.biochem.73.011303.073823.
Howard J, Hyman AA. Dynamics and mechanics of the microtubule plus end. Nature. 2003;422(6933):753–8. https://doi.org/10.1038/nature01600.
Vavylonis D, Yang Q, O’Shaughnessy B. Actin polymerization kinetics, cap structure, and fluctuations. Proc Natl Acad Sci U S A. 2005;102(24):8543–8. https://doi.org/10.1073/pnas.0501435102.
Footer MJ, Kerssemakers JWJ, Theriot JA, et al. Direct measurement of force generation by actin filament polymerization using an optical trap. Proc Natl Acad Sci U S A. 2007;104(7):2181–6. https://doi.org/10.1073/pnas.0607052104.
Howard J. Mechanics of motor proteins and the cytoskeleton. Sunderland: Sinauer Associates; 2006.
Lockot HW, Uhlig S. Bibliographia aethiopica, Aethiopistische forschungen, vol. 41. Wiesbaden: Steiner; 1998.
Bell A, Macfarquhar C. Encyclopaedia britannica: or, a dictionary of arts and sciences, three volumes. Scotland: Edinburgh; 1771.
Borel F, Taylor JB, Paris IM. The splendor of ethnic jewelry: from the Colette and Jean-Pierre Ghysels collection, Pbk. ed. New York: H. N. Abrams; 2001
Mahaffy RE, Shih CK, MacKintosh FC, et al. Scanning probe-based frequency-dependent microrheology of polymer gels and biological cells. Phys Rev Lett. 2000;85(4):880–3. https://doi.org/10.1103/PhysRevLett.85.880.
Chen EJ, Novakofski J, Jenkins WK, et al. Young’s modulus measurements of soft tissues with application to elasticity imaging. IEEE Trans Ultrason Ferroelect Freq Contr. 1996;43(1):191–4. https://doi.org/10.1109/58.484478.
Rho J-Y, Kuhn-Spearing L, Zioupos P. Mechanical properties and the hierarchical structure of bone. Med Eng Phys. 1998;20(2):92–102. https://doi.org/10.1016/S1350-4533(98)00007-1.
Rho JY, Ashman RB, Turner CH. Young’s modulus of trabecular and cortical bone material: ultrasonic and microtensile measurements. J Biomech. 1993;26(2):111–9. https://doi.org/10.1016/0021-9290(93)90042-D.
Akhtar R, Sherratt MJ, Cruickshank JK, et al. Characterizing the elastic properties of tissues. Mater Today. 2011;14(3):96–105. https://doi.org/10.1016/S1369-7021(11)70059-1.
Yanniotis S, Skaltsi S, Karaburnioti S. Effect of moisture content on the viscosity of honey at different temperatures. J Food Eng. 2006;72(4):372–7. https://doi.org/10.1016/j.jfoodeng.2004.12.017.
Kesmarky G, Kenyeres P, Rabai M, et al. Plasma viscosity: a forgotten variable. Clin Hemorheol Microcirc. 2008;39(1-4):243–6.
Zhou EH, Martinez FD, Fredberg JJ. Cell rheology: mush rather than machine. Nat Mater. 2013;12(3):184. https://doi.org/10.1038/nmat3574.
Spence AJ. Scaling in biology. Curr Biol. 2009;19(2):R57–61. https://doi.org/10.1016/j.cub.2008.10.042.
Brown JH, West GB, editors. Scaling in biology. Santa Fe Institute studies in the sciences of complexity. Oxford: Oxford University Press; 2000.
West GB. A general model for the origin of allometric scaling laws in biology. Science. 1997;276(5309):122–6. https://doi.org/10.1126/science.276.5309.122.
Kollmannsberger P, Fabry B. Linear and nonlinear rheology of living cells. Annu Rev Mater Res. 2011;41(1):75–97. https://doi.org/10.1146/annurev-matsci-062910-100351.
Sandersius SA, Newman TJ. Modeling cell rheology with the subcellular element model. Phys Biol. 2008;5(1):15002. https://doi.org/10.1088/1478-3975/5/1/015002.
Fabry B, Maksym GN, Butler JP, et al. Scaling the microrheology of living cells. Phys Rev Lett. 2001;87(14):148102. https://doi.org/10.1103/PhysRevLett.87.148102.
Chen DT, Wen Q, Janmey PA, et al. Rheology of Soft materials. Annu Rev Condens Matter Phys. 2010;1(1):301–22. https://doi.org/10.1146/annurev-conmatphys-070909-104120.
Kroy K. Dynamics of wormlike and glassy wormlike chains. Soft Matter. 2008;4(12):2323. https://doi.org/10.1039/B807018K.
Kroy K, Glaser J. The glassy wormlike chain. New J Phys. 2007;9(11):416. https://doi.org/10.1088/1367-2630/9/11/416.
Wolff L, Fernandez P, Kroy K. Resolving the stiffening-softening paradox in cell mechanics. PLoS One. 2012;7(7):e40063. https://doi.org/10.1371/journal.pone.0040063.
Rodriguez ML, McGarry PJ, Sniadecki NJ. Review on cell mechanics: experimental and modeling approaches. Appl Mech Rev. 2013;65(6):60801. https://doi.org/10.1115/1.4025355.
Lim CT, Zhou EH, Quek ST. Mechanical models for living cells—a review. J Biomech. 2006;39(2):195–216. https://doi.org/10.1016/j.jbiomech.2004.12.008.
Herant M, Marganski WA, Dembo M. The mechanics of neutrophils: synthetic modeling of three experiments. Biophys J. 2003;84(5):3389–413. https://doi.org/10.1016/S0006-3495(03)70062-9.
Dai J, Ting-Beall HP, Hochmuth RM, et al. Myosin I contributes to the generation of resting cortical tension. Biophys J. 1999;77(2):1168–76.
Peskin CS, Odell GM, Oster GF. Cellular motions and thermal fluctuations: the Brownian ratchet. Biophys J. 1993;65(1):316–24. https://doi.org/10.1016/S0006-3495(93)81035-X.
Mogilner A, Oster G. Cell motility driven by actin polymerization. Biophys J. 1996;71(6):3030–45. https://doi.org/10.1016/S0006-3495(96)79496-1.
Kuusela E, Alt W. Continuum model of cell adhesion and migration. J Math Biol. 2009;58(1-2):135–61. https://doi.org/10.1007/s00285-008-0179-x.
Zimmerle CT, Frieden C. Effect of temperature on the mechanism of actin polymerization. Biochemistry. 1986;25(21):6432–8.
Kis A, Kasas S, Kulik AJ, et al. Temperature-dependent elasticity of microtubules. Langmuir. 2008;24(12):6176–81. https://doi.org/10.1021/la800438q.
Yengo CM, Takagi Y, Sellers JR. Temperature dependent measurements reveal similarities between muscle and non-muscle myosin motility. J Muscle Res Cell Motil. 2012;33(6):385–94. https://doi.org/10.1007/s10974-012-9316-7.
Oroian M, Amariei S, Escriche I, et al. A viscoelastic model for honeys using the time–temperature superposition principle (TTSP). Food Bioprocess Technol. 2013;6(9):2251–60. https://doi.org/10.1007/s11947-012-0893-7.
Kießling TR, Stange R, Käs JA, et al. Thermorheology of living cells—impact of temperature variations on cell mechanics. New J Phys. 2013;15(4):45026. https://doi.org/10.1088/1367-2630/15/4/045026.
Schmidt BUS, Kießling TR, Warmt E, et al. Complex thermorheology of living cells. New J Phys. 2015;17(7):73010. https://doi.org/10.1088/1367-2630/17/7/073010.
Joanny J, Prost J. Active gels as a description of the actin-myosin cytoskeleton. HFSP J. 2009;3(2):94–104. https://doi.org/10.2976/1.3054712.
Joanny J-F, Ramaswamy S. A drop of active matter. J Fluid Mech. 2012;705:46–57. https://doi.org/10.1017/jfm.2012.131.
Pearson JE. Complex patterns in a simple system. Science. 1993;261(5118):189–92. https://doi.org/10.1126/science.261.5118.189.
Strehle D, Schnauss J, Heussinger C, et al. Transiently crosslinked F-actin bundles. Eur Biophys J. 2011;40(1):93–101. https://doi.org/10.1007/s00249-010-0621-z.
Goldman RD, Khuon S, Chou YH, et al. The function of intermediate filaments in cell shape and cytoskeletal integrity. J Cell Biol. 1996;134(4):971–83.
Pourati J, Maniotis A, Spiegel D, et al. Is cytoskeletal tension a major determinant of cell deformability in adherent endothelial cells? Am J Physiol. 1998;274(5 Pt 1):C1283–9.
Wang N, Im T-N, Chen J, et al. Cell prestress. I. Stiffness and prestress are closely associated in adherent contractile cells. Am J Physiol Cell Physiol. 2002;282(3):C606–16. https://doi.org/10.1152/ajpcell.00269.2001.
Fernandez P, Pullarkat PA, Ott A. A master relation defines the nonlinear viscoelasticity of single fibroblasts. Biophys J. 2006;90(10):3796–805. https://doi.org/10.1529/biophysj.105.072215.
Trepat X, Deng L, An SS, et al. Universal physical responses to stretch in the living cell. Nature. 2007;447(7144):592–5. https://doi.org/10.1038/nature05824.
Krishnan R, Park CY, Lin YC, et al. Reinforcement versus fluidization in cytoskeletal mechanoresponsiveness. PLoS One. 2009;4(5):e5486. https://doi.org/10.1371/journal.pone.0005486.
Wolf K, Te Lindert M, Krause M, et al. Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force. J Cell Biol. 2013;201(7):1069–84. https://doi.org/10.1083/jcb.201210152.
Lange JR, Steinwachs J, Kolb T, et al. Microconstriction arrays for high-throughput quantitative measurements of cell mechanical properties. Biophys J. 2015;109(1):26–34. https://doi.org/10.1016/j.bpj.2015.05.029.
Friedl P, Wolf K, Lammerding J. Nuclear mechanics during cell migration. Curr Opin Cell Biol. 2011;23(1):55–64. https://doi.org/10.1016/j.ceb.2010.10.015.
Dahl KN, Ribeiro AJ, Lammerding J. Nuclear shape, mechanics, and mechanotransduction. Circ Res. 2008;102(11):1307–18. https://doi.org/10.1161/CIRCRESAHA.108.173989.
Swift J, Discher DE. The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue. J Cell Sci. 2014;127(Pt 14):3005–15. https://doi.org/10.1242/jcs.149203.
Harada T, Swift J, Irianto J, et al. Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J Cell Biol. 2014;204(5):669–82. https://doi.org/10.1083/jcb.201308029.
Händel C, Schmidt BUS, Schiller J, et al. Cell membrane softening in human breast and cervical cancer cells. New J Phys. 2015;17(8):83008. https://doi.org/10.1088/1367-2630/17/8/083008.
Braig S, Schmidt BUS, Stoiber K, et al. Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion. New J Phys. 2015;17(8):83007. https://doi.org/10.1088/1367-2630/17/8/083007.
Gracià RS, Bezlyepkina N, Knorr RL, et al. Effect of cholesterol on the rigidity of saturated and unsaturated membranes: fluctuation and electrodeformation analysis of giant vesicles. Soft Matter. 2010;6(7):1472. https://doi.org/10.1039/b920629a.
Lu Y-B, Franze K, Seifert G, et al. Viscoelastic properties of individual glial cells and neurons in the CNS. Proc Natl Acad Sci U S A. 2006;103(47):17759–64. https://doi.org/10.1073/pnas.0606150103.
Radmacher M, Fritz M, Kacher CM, et al. Measuring the viscoelastic properties of human platelets with the atomic force microscope. Biophys J. 1996;70(1):556–67. https://doi.org/10.1016/S0006-3495(96)79602-9.
Radmacher M. Studying the mechanics of cellular processes by atomic force microscopy. In:Cell mechanics, vol. 83. London: Elsevier; 2007. p. 347–72.
Janmey PA, Winer JP, Murray ME, et al. The hard life of soft cells. Cell Motil Cytoskeleton. 2009;66(8):597–605. https://doi.org/10.1002/cm.20382.
Mierke CT, Rosel D, Fabry B, et al. Contractile forces in tumor cell migration. Eur J Cell Biol. 2008;87(8-9):669–76. https://doi.org/10.1016/j.ejcb.2008.01.002.
Engler AJ, Sen S, Sweeney HL, et al. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126(4):677–89. https://doi.org/10.1016/j.cell.2006.06.044.
Fritsch A, Höckel M, Kiessling T, et al. Are biomechanical changes necessary for tumour progression? Nat Phys. 2010;6(10):730–2. https://doi.org/10.1038/nphys1800.
Thery M, Bornens M. Cell shape and cell division. Curr Opin Cell Biol. 2006;18(6):648–57. https://doi.org/10.1016/j.ceb.2006.10.001.
Yeung T, Georges PC, Flanagan LA, et al. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motil Cytoskeleton. 2005;60(1):24–34. https://doi.org/10.1002/cm.20041.
Thoumine O, Cardoso O, Meister J-J. Changes in the mechanical properties of fibroblasts during spreading: a micromanipulation study. Eur Biophys J. 1999;28(3):222–34. https://doi.org/10.1007/s002490050203.
Wottawah F, Schinkinger S, Lincoln B, et al. Optical rheology of biological cells. Phys Rev Lett. 2005;94(9):98103. https://doi.org/10.1103/PhysRevLett.94.098103.
Schmid-Schönbein GW, Sung KL, Tözeren H, et al. Passive mechanical properties of human leukocytes. Biophys J. 1981;36(1):243–56. https://doi.org/10.1016/S0006-3495(81)84726-1.
Thoumine O, Ott A. Comparison of the mechanical properties of normal and transformed fibroblasts. Biorheology. 1997;34(4-5):309–26. https://doi.org/10.1016/S0006-355X(98)00007-9.
Mahaffy RE, Park S, Gerde E, et al. Quantitative analysis of the viscoelastic properties of thin regions of fibroblasts using atomic force microscopy. Biophys J. 2004;86(3):1777–93. https://doi.org/10.1016/S0006-3495(04)74245-9.
Alcaraz J, Buscemi L, Grabulosa M, et al. Microrheology of human lung epithelial cells measured by atomic force microscopy. Biophys J. 2003;84(3):2071–9. https://doi.org/10.1016/S0006-3495(03)75014-0.
Mizuno D, Bacabac R, Tardin C, et al. High-resolution probing of cellular force transmission. Phys Rev Lett. 2009;102(16):168102. https://doi.org/10.1103/PhysRevLett.102.168102.
Hoffman BD, Massiera G, van Citters KM, et al. The consensus mechanics of cultured mammalian cells. Proc Natl Acad Sci U S A. 2006;103(27):10259–64. https://doi.org/10.1073/pnas.0510348103.
Yamada S, Wirtz D, Kuo SC. Mechanics of living cells measured by laser tracking microrheology. Biophys J. 2000;78(4):1736–47. https://doi.org/10.1016/S0006-3495(00)76725-7.
Crocker JC, Valentine MT, Weeks ER, et al. Two-point microrheology of inhomogeneous soft materials. Phys Rev Lett. 2000;85(4):888–91. https://doi.org/10.1103/PhysRevLett.85.888.
Fabry B, Maksym GN, Butler JP, et al. Time scale and other invariants of integrative mechanical behavior in living cells. Phys Rev E Stat Nonlin Soft Matter Phys. 2003;68(4 Pt 1):41914. https://doi.org/10.1103/PhysRevE.68.041914.
Guck J, Ananthakrishnan R, Moon TJ, et al. Optical deformability of soft biological dielectrics. Phys Rev Lett. 2000;84(23):5451–4. https://doi.org/10.1103/PhysRevLett.84.5451.
Guck J, Ananthakrishnan R, Mahmood H, et al. The optical stretcher: a novel laser tool to micromanipulate cells. Biophys J. 2001;81(2):767–84. https://doi.org/10.1016/S0006-3495(01)75740-2.
Brunner C, Niendorf A, Käs JA. Passive and active single-cell biomechanics: a new perspective in cancer diagnosis. Soft Matter. 2009;5(11):2171. https://doi.org/10.1039/b807545j.
Mietke A, Otto O, Girardo S, et al. Extracting cell stiffness from real-time deformability cytometry: theory and experiment. Biophys J. 2015;109(10):2023–36. https://doi.org/10.1016/j.bpj.2015.09.006.
Otto O, Rosendahl P, Mietke A, et al. Real-time deformability cytometry: on-the-fly cell mechanical phenotyping. Nat Methods. 2015;12(3):199–202. https://doi.org/10.1038/nmeth.3281.
Gossett DR, Tse HTK, Lee SA, et al. Hydrodynamic stretching of single cells for large population mechanical phenotyping. Proc Natl Acad Sci U S A. 2012;109(20):7630–5. https://doi.org/10.1073/pnas.1200107109.
Evans EA. Bending elastic modulus of red blood cell membrane derived from buckling instability in micropipet aspiration tests. Biophys J. 1983;43(1):27–30. https://doi.org/10.1016/S0006-3495(83)84319-7.
Schulze C, Muller K, Kas JA, et al. Compaction of cell shape occurs before decrease of elasticity in CHO-K1 cells treated with actin cytoskeleton disrupting drug cytochalasin D. Cell Motil Cytoskeleton. 2009;66(4):193–201. https://doi.org/10.1002/cm.20341.
Jonas O, Duschl C. Force propagation and force generation in cells. Cytoskeleton. 2010;67(9):555–63. https://doi.org/10.1002/cm.20466.
Fuhs T, Reuter L, Vonderhaid I, et al. Inherently slow and weak forward forces of neuronal growth cones measured by a drift-stabilized atomic force microscope. Cytoskeleton. 2013;70(1):44–53. https://doi.org/10.1002/cm.21080.
Thoumine O, Ott A, Cardoso O, et al. Microplates: a new tool for manipulation and mechanical perturbation of individual cells. J Biochem Biophys Methods. 1999;39(1-2):47–62. https://doi.org/10.1016/S0165-022X(98)00052-9.
Fernandez P, Ott A. Single cell mechanics: stress stiffening and kinematic hardening. Phys Rev Lett. 2008;100(23):238102. https://doi.org/10.1103/PhysRevLett.100.238102.
Benoit M, Gabriel D, Gerisch G, et al. Discrete interactions in cell adhesion measured by single-molecule force spectroscopy. Nat Cell Biol. 2000;2(6):313–7. https://doi.org/10.1038/35014000.
Hoffman BD, Crocker JC. Cell mechanics: dissecting the physical responses of cells to force. Annu Rev Biomed Eng. 2009;11:259–88. https://doi.org/10.1146/annurev.bioeng.10.061807.160511.
Golde T, Schuldt C, Schnauss J, et al. Fluorescent beads disintegrate actin networks. Phys Rev E Stat Nonlinear Soft Matter Phys. 2013;88(4):44601. https://doi.org/10.1103/PhysRevE.88.044601.
Levine L. One- and two-particle microrheology. Phys Rev Lett. 2000;85(8):1774–7. https://doi.org/10.1103/PhysRevLett.85.1774.
Lau AWC, Hoffman BD, Davies A, et al. Microrheology, stress fluctuations, and active behavior of living cells. Phys Rev Lett. 2003;91(19):198101. https://doi.org/10.1103/PhysRevLett.91.198101.
Mijailovich SM, Kojic M, Zivkovic M, et al. A finite element model of cell deformation during magnetic bead twisting. J Appl Physiol. 2002;93(4):1429–36. https://doi.org/10.1152/japplphysiol.00255.2002.
Massiera G, van Citters KM, Biancaniello PL, et al. Mechanics of single cells: rheology, time dependence, and fluctuations. Biophys J. 2007;93(10):3703–13. https://doi.org/10.1529/biophysj.107.111641.
Kreysing MK, Kießling T, Fritsch A, et al. The optical cell rotator. Opt Express. 2008;16(21):16984. https://doi.org/10.1364/OE.16.016984.
Gyger M, Stange R, Kiessling TR, et al. Active contractions in single suspended epithelial cells. Eur Biophys J. 2014;43(1):11–23. https://doi.org/10.1007/s00249-013-0935-8.
Maloney JM, Lehnhardt E, Long AF, et al. Mechanical fluidity of fully suspended biological cells. Biophys J. 2013;105(8):1767–77. https://doi.org/10.1016/j.bpj.2013.08.040.
Maloney JM, van Vliet KJ. Chemoenvironmental modulators of fluidity in the suspended biological cell. Soft Matter. 2014;10(40):8031–42. https://doi.org/10.1039/C4SM00743C.
van Vliet K, Bao G, Suresh S. The biomechanics toolbox: Experimental approaches for living cells and biomolecules. Acta Mater. 2003;51(19):5881–905. https://doi.org/10.1016/j.actamat.2003.09.001.
Pullarkat P, Fernandez P, Ott A. Rheological properties of the eukaryotic cell cytoskeleton. Phys Rep. 2007;449(1-3):29–53. https://doi.org/10.1016/j.physrep.2007.03.002.
Fernández P, Heymann L, Ott A, et al. Shear rheology of a cell monolayer. New J Phys. 2007;9(11):419. https://doi.org/10.1088/1367-2630/9/11/419.
Deng L, Trepat X, Butler JP, et al. Fast and slow dynamics of the cytoskeleton. Nat Mater. 2006;5(8):636–40. https://doi.org/10.1038/nmat1685.
Weihs D, Mason TG, Teitell MA. Bio-microrheology: a frontier in microrheology. Biophys J. 2006;91(11):4296–305. https://doi.org/10.1529/biophysj.106.081109.
Roth KB, Neeves KB, Squier J, et al. High-throughput linear optical stretcher for mechanical characterization of blood cells. Cytometry A. 2016;89(4):391–7. https://doi.org/10.1002/cyto.a.22794.
Szabó B, Szöllösi GJ, Gönci B, et al. Phase transition in the collective migration of tissue cells: experiment and model. Phys Rev E. 2006;74(6):61908. https://doi.org/10.1103/PhysRevE.74.061908.
Deisboeck TS, Couzin ID. Collective behavior in cancer cell populations. BioEssays. 2009;31(2):190–7. https://doi.org/10.1002/bies.200800084.
Sander EE, van Delft S, ten KJP, et al. Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. J Cell Biol. 1998;143(5):1385–98.
Wu Y, Kanchanawong P, Zaidel-Bar R. Actin-delimited adhesion-independent clustering of E-cadherin forms the nanoscale building blocks of adherens junctions. Dev Cell. 2015;32(2):139–54. https://doi.org/10.1016/j.devcel.2014.12.003.
Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420–8. https://doi.org/10.1172/JCI39104.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70. https://doi.org/10.1016/S0092-8674(00)81683-9.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74. https://doi.org/10.1016/j.cell.2011.02.013.
Ma L, Young J, Prabhala H, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12(3):247–56. https://doi.org/10.1038/ncb2024.
Plutoni C, Bazellieres E, Le Borgne-Rochet M, et al. P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces. J Cell Biol. 2016;212(2):199–217. https://doi.org/10.1083/jcb.201505105.
Gaggioli C, Hooper S, Hidalgo-Carcedo C, et al. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol. 2007;9(12):1392–400. https://doi.org/10.1038/ncb1658.
Ladoux B, Mege R-M, Trepat X. Front-rear polarization by mechanical cues: from single cells to tissues. Trends Cell Biol. 2016;26(6):420–33. https://doi.org/10.1016/j.tcb.2016.02.002.
Mierke CT. The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion. New J Phys. 2013;15(1):15003. https://doi.org/10.1088/1367-2630/15/1/015003.
Seftor RE, Seftor EA, Gehlsen KR, et al. Role of the alpha v beta 3 integrin in human melanoma cell invasion. Proc Natl Acad Sci U S A. 1992;89(5):1557–61. https://doi.org/10.1073/pnas.89.5.1557.
Aoudjit F, Vuori K. Integrin signaling inhibits paclitaxel-induced apoptosis in breast cancer cells. Oncogene. 2001;20(36):4995–5004. https://doi.org/10.1038/sj.onc.1204554.
Munger JS, Huang X, Kawakatsu H, et al. A mechanism for regulating pulmonary inflammation and fibrosis: the integrin αvβ6 binds and activates latent TGF β1. Cell. 1999;96(3):319–28. https://doi.org/10.1016/S0092-8674(00)80545-0.
Soldi R, Mitola S, Strasly M, et al. Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. EMBO J. 1999;18(4):882–92. https://doi.org/10.1093/emboj/18.4.882.
Bissell MJ, Radisky DC, Rizki A, et al. The organizing principle: microenvironmental influences in the normal and malignant breast. Differentiation. 2002;70(9-10):537–46. https://doi.org/10.1046/j.1432-0436.2002.700907.x.
Dvorak HF, Weaver VM, Tlsty TD, et al. Tumor microenvironment and progression. J Surg Oncol. 2011;103(6):468–74. https://doi.org/10.1002/jso.21709.
Heine P, Ehrlicher A, Käs J. Neuronal and metastatic cancer cells: unlike brothers. Biochim Biophys Acta Mol Cell Res. 2015;1853(11):3126–31. https://doi.org/10.1016/j.bbamcr.2015.06.011.
Ibragimova I, de Cáceres II, Hoffman AM, et al. Global Reactivation of Epigenetically Silenced Genes in Prostate Cancer. Cancer Prev Res (Phila). 2010;3(9):1084–92. https://doi.org/10.1158/1940-6207.CAPR-10-0039.
Karpf AR, Jones DA. Reactivating the expression of methylation silenced genes in human cancer. Oncogene. 2002;21(35):5496–503. https://doi.org/10.1038/sj.onc.1205602.
Cameron EE, Bachman KE, Myohanen S, et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet. 1999;21(1):103–7. https://doi.org/10.1038/5047.
Riek K, Klatt D, Nuzha H, et al. Wide-range dynamic magnetic resonance elastography. J Biomech. 2011;44(7):1380–6. https://doi.org/10.1016/j.jbiomech.2010.12.031.
Bi D, Yang X, Marchetti MC, et al. Motility-driven glass and jamming transitions in biological tissues. Phys Rev X. 2016;6(2):021011. https://doi.org/10.1103/PhysRevX.6.021011.
Bi D, Lopez JH, Schwarz JM, et al. A density-independent rigidity transition in biological tissues. Nat Phys. 2015;11(12):1074–9. https://doi.org/10.1038/NPHYS3471.
Angelini TE, Hannezo E, Trepat X, et al. Glass-like dynamics of collective cell migration. Proc Natl Acad Sci U S A. 2011;108(12):4714–9. https://doi.org/10.1073/pnas.1010059108.
Bi D, Lopez JH, Schwarz JM, et al. Energy barriers and cell migration in densely packed tissues. Soft Matter. 2014;10(12):1885–90. https://doi.org/10.1039/c3sm52893f.
Farhadifar R, Roper J-C, Aigouy B, et al. The influence of cell mechanics, cell-cell interactions, and proliferation on epithelial packing. Curr Biol. 2007;17(24):2095–104. https://doi.org/10.1016/j.cub.2007.11.049.
Basan M, Prost J, Joanny J-F, et al. Dissipative particle dynamics simulations for biological tissues: rheology and competition. Phys Biol. 2011;8(2):26014. https://doi.org/10.1088/1478-3975/8/2/026014.
Podewitz N, Jülicher F, Gompper G, et al. Interface dynamics of competing tissues. New J Phys. 2016;18(8):83020. https://doi.org/10.1088/1367-2630/18/8/083020.
Zhu Y, Dong Z, Wejinya UC, et al. Determination of mechanical properties of soft tissue scaffolds by atomic force microscopy nanoindentation. J Biomech. 2011;44(13):2356–61. https://doi.org/10.1016/j.jbiomech.2011.07.010.
Schuldt C, Karl A, Korber N, et al. Dose-dependent collagen cross-linking of rabbit scleral tissue by blue light and riboflavin treatment probed by dynamic shear rheology. Acta Ophthalmol. 2015;93(5):e328–36. https://doi.org/10.1111/aos.12621.
Reiss-Zimmermann M, Streitberger K-J, Sack I, et al. High resolution imaging of viscoelastic properties of intracranial tumours by multi-frequency magnetic resonance elastography. Clin Neuroradiol. 2015;25(4):371–8. https://doi.org/10.1007/s00062-014-0311-9.
Steinberg MS. On the mechanism of tissue reconstruction by dissociated cells. I. Population kinetics, differential adhesiveness. and the absence of directed migration. Proc Natl Acad Sci. 1962;48(9):1577–82. https://doi.org/10.1073/pnas.48.9.1577.
Foty RA, Steinberg MS. The differential adhesion hypothesis: a direct evaluation. Dev Biol. 2005;278(1):255–63. https://doi.org/10.1016/j.ydbio.2004.11.012.
Pawlizak S, Fritsch AW, Grosser S, et al. Testing the differential adhesion hypothesis across the epithelial−mesenchymal transition. New J Phys. 2015;17(8):83049. https://doi.org/10.1088/1367-2630/17/8/083049.
Albini A, Iwamoto Y, Kleinman HK, et al. A rapid in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res. 1987;47(12):3239–45.
Paszek MJ, Zahir N, Johnson KR, et al. Tensional homeostasis and the malignant phenotype. Cancer Cell. 2005;8(3):241–54. https://doi.org/10.1016/j.ccr.2005.08.010.
Young JS, Llumsden CE, Stalker AL. The significance of the “tissue pressure” of normal testicular and of neoplastic (Brown-Pearce carcinoma) tissue in the rabbit. J Pathol. 1950;62(3):313–33. https://doi.org/10.1002/path.1700620303.
Plodinec M, Loparic M, Monnier CA, et al. The nanomechanical signature of breast cancer. Nat Nanotechnol. 2012;7(11):757–65. https://doi.org/10.1038/nnano.2012.167.
Nnetu KD, Knorr M, Käs J, et al. The impact of jamming on boundaries of collectively moving weak-interacting cells. New J Phys. 2012;14(11):115012. https://doi.org/10.1088/1367-2630/14/11/115012.
Mouw JK, Yui Y, Damiano L, et al. Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nat Med. 2014;20(4):360–7. https://doi.org/10.1038/nm.3497.
Haeger A, Krause M, Wolf K, et al. Cell jamming: collective invasion of mesenchymal tumor cells imposed by tissue confinement. Biochim Biophys Acta. 2014;1840(8):2386–95. https://doi.org/10.1016/j.bbagen.2014.03.020.
Park J-A, Kim JH, Bi D, et al. Unjamming and cell shape in the asthmatic airway epithelium. Nat Mater. 2015;14(10):1040–8. https://doi.org/10.1038/nmat4357.
Farina KL, Wyckoff JB, Rivera J, et al. Cell motility of tumor cells visualized in living intact primary tumors using green fluorescent protein. Cancer Res. 1998;58(12):2528–32.
Wang Y-L, Discher DE, editors. Cell mechanics, Methods in cell biology. London: Elsevier; 2007.
Diggs LW. Pathology of sickle cell disease. JAMA. 1971;218(4):600. https://doi.org/10.1001/jama.1971.03190170078040.
Platt OS. Sickle cell anemia as an inflammatory disease. J Clin Invest. 2000;106(3):337–8. https://doi.org/10.1172/JCI10726.
Weinberg RA. The biology of cancer. 2nd ed. New York: Garland Science; 2014.
Seltmann K, Fritsch AW, Käs JA, et al. Keratins significantly contribute to cell stiffness and impact invasive behavior. Proc Natl Acad Sci U S A. 2013;110(46):18507–12. https://doi.org/10.1073/pnas.1310493110.
Cross SE, Jin Y-S, Tondre J, et al. AFM-based analysis of human metastatic cancer cells. Nanotechnology. 2008;19(38):384003. https://doi.org/10.1088/0957-4484/19/38/384003.
Lichtman MA. Rheology of leukocytes, leukocyte suspensions, and blood in leukemia possible relationship to clinical manifestations. J Clin Invest. 1973;52(2):350–8.
Baker EL, Bonnecaze RT, Zaman MH. Extracellular matrix stiffness and architecture govern intracellular rheology in cancer. Biophys J. 2009;97(4):1013–21. https://doi.org/10.1016/j.bpj.2009.05.054.
Mofrad MR. Rheology of the cytoskeleton. Annu Rev Fluid Mech. 2009;41(1):433–53. https://doi.org/10.1146/annurev.fluid.010908.165236.
Guck J, Schinkinger S, Lincoln B, et al. Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence. Biophys J. 2005;88(5):3689–98. https://doi.org/10.1529/biophysj.104.045476.
Merkel M, Manning ML. Using cell deformation and motion to predict forces and collective behavior in morphogenesis. Semin Cell Dev Biol. 2016;67:167. https://doi.org/10.1016/j.semcdb.2016.07.029.
Manning ML, Collins E-MS. Focus on physical models in biology: multicellularity and active matter. New J Phys. 2015;17(4):40201. https://doi.org/10.1088/1367-2630/17/4/040201.
Pegoraro AF, Fredberg JJ, Park J-A. Problems in biology with many scales of length: cell–cell adhesion and cell jamming in collective cellular migration. Exp Cell Res. 2016;343(1):54–9. https://doi.org/10.1016/j.yexcr.2015.10.036.
Weigelin B, Friedl P. Cancer cells: stemness shaped by curvature. Nat Mater. 2016;15(8):827–8. https://doi.org/10.1038/nmat4711.
Te Boekhorst V, Preziosi L, Friedl P. Plasticity of cell migration in vivo and in silico. Annu Rev Cell Dev Biol. 2016;32:491–526. https://doi.org/10.1146/annurev-cellbio-111315-125201.
Collins C, Nelson WJ. Running with neighbors: coordinating cell migration and cell–cell adhesion. Cell Adhes Migr. 2015;36:62–70. https://doi.org/10.1016/j.ceb.2015.07.004.
Kashef J, Franz CM. Quantitative methods for analyzing cell–cell adhesion in development. Dev Biol. 2015;401(1):165–74. https://doi.org/10.1016/j.ydbio.2014.11.002.
Acknowledgments
We thank Till Möhn, Jürgen Lippoldt, Martin Glaser and Benjamin Wolf for their very helpful comments, discussions, advices for illustrations, and language editing.
Glossary
Self-organization: Self-organization is an active, non-equilibrium process of an open system where energy is constantly dissipated and needs to be resupplied, for instance, to generate forces (such as the actin–myosin power stroke) or to organize dynamic structures (such as the lamellipodium for cell migration) far from the thermodynamic equilibrium [10].
Self-assembly: Self-assembly processes are solely based on equilibrium dynamics and are independent of energy dissipation. They occur spontaneously and tend to minimize the free energy of the system driving it toward its thermodynamic equilibrium without an additional energy source such as ATP or GTP. Self-assembly can occur in closed systems [10].
Persistence Length: Mechanical property quantifying the stiffness of a polymer relative to its length. The length scale on which the direction vectors of both ends of a filament lose their correlation.
Bending Stiffness: The resistance of a beam with unit diameter and length while undergoing bending. The higher the bending stiffness, the harder to flex the unit beam.
Molecular Motors: Molecular machines which consume energy (e.g., ATP, GTP) and convert it into motion or mechanical work.
Treadmilling: Steady-state phenomenon of cytoskeletal filaments, mostly actin, where one filament end depolymerizes and the other end polymerizes, leading to shrinkage and growth at the ends with no net length change of the filament.
Tensile Creep Compliance: The magnitude of the creep response of a unit bulk material for a given unit force load. The higher the tensile creep compliance, the easier it deforms under force load.
Elastic Modulus (Young’s Modulus) or Shear Modulus: The resistance of a unit bulk material under axial load or under shearing load, respectively. The higher the elastic modulus or shear modulus, the harder to deform the material. In incompressible materials, the elastic modulus is three times the shear modulus.
Exocytosis: Active transport of molecules out of the cell via a secretory vesicle as transport carrier.
Endocytosis: Active transport of molecules into the cell via encapsulation of the molecules with the cell membrane and formation of a vesicle as transport carrier.
Receptor Binding: Binding of signaling molecules to transmembrane proteins used for cellular and tissue response.
Mechanosignaling: Sensing and signaling of cells induce a response to mechanical, environmental cues.
Glass-like Material: Solid-phase state of a material, where the strong, noncrystalline entanglement of the molecules, usually polymer chains, prevents an unhindered liquid-like flow and movement of the molecules for low thermal energy. Above the glass transition temperature, the material can flow again.
Amorphous Material: Noncrystalline solid with no long-range order, usually consisting of many clustered domains with different (crystalline) orientations and substructures.
Yield Stress Fluid: A fluid which only starts to flow above a critical stress, the yield stress. For stresses below the yield stress, it behaves like a solid.
Homeostatic Stress: Internal stress of a tissue generated by adhesion forces, which is actively regulated to remain close to constant.
Differential Adhesion Hypothesis: Hypothesis for cellular movement in tissues of different cell types based on thermodynamic principles. Cells with different adhesion forces will minimize their free energy by moving to other cells with similar adhesion forces in order to maximize bonding strength.
Jamming: A quasi-phase transition of a material, where rigidity suddenly increases and fluidity suddenly decreases when the density of cells (or molecules) increases above a critical level.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this chapter
Cite this chapter
Kubitschke, H., Morawetz, E.W., Käs, J.A., Schnauß, J. (2018). Physical Properties of Single Cells and Collective Behavior. In: Sack, I., Schaeffter, T. (eds) Quantification of Biophysical Parameters in Medical Imaging. Springer, Cham. https://doi.org/10.1007/978-3-319-65924-4_5
Download citation
DOI: https://doi.org/10.1007/978-3-319-65924-4_5
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-65923-7
Online ISBN: 978-3-319-65924-4
eBook Packages: MedicineMedicine (R0)