Abstract
Cells interact with their extracellular environment, from which they gather information that influences their behaviour. The cytoskeleton provides a bridge to transmit information between the extracellular and the intracellular environments. It has been suggested that the CSK components may have distinct mechanical roles in the cell and that they might form the structure that defines cell rigidity. One approach to studying the mechanosensing processes is to understand the mechanical properties of cells’ constitutive components individually. In this chapter we describe the development of a multi-structural 3D finite element model of a single-adherent cell to investigate the biophysical differences of the mechanical role of each cytoskeleton component. The model includes prestressed actin bundles and microtubule within the cytoplasm and nucleus, which are surrounded by the actin cortex.
With the multi-structural model, we predicted that actin cortex and microtubules were targeted to respond to compressive loads, while actin bundles and microtubules were major components in maintaining cell forces during stretching. Additionally, corroboration of the multi-structural model regarding its ability to identify the role of the CSK components was obtained by comparing the numerical predictions with AFM force measurements on U2OS-osteosarcoma cells exposed to different cytoskeleton-disrupting drugs. Overall, the multi-structural model not only illustrates that a combination of cytoskeletal structures with their own properties is necessary for a complete description of cellular mechanics but also clarifies the effects of cytoskeletal heterogeneity on the interpretation of force-deformation measurements.
This chapter forms part the PhD thesis of Sara Barreto available here: http://etheses.whiterose.ac.uk/4928/
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References
Barreto S (2013) Biomechanical study of the mechanical and structural properties of adherent cells. University of Sheffield
Barreto S, Casper HC, Perrault CM, Fletcher DA, Lacroix D (2013) A multi-structural single cell model of force-induced interactions of cytoskeletal components. Biomaterials 34(26):6119–6126. https://doi.org/10.1016/j.biomaterials.2013.04.022
Barreto S, Perrault CM, Lacroix D (2014) Structural finite element analysis to explain cell mechanics variability. J Mech Behav Biomed Mater 38:219–231. https://doi.org/10.1016/j.jmbbm.2013.11.022
Bausch AR, Ziemann F, Boulbitch AA, Jacobson K, Sackmann E (1998) Local measurements of viscoelastic parameters of adherent cell surfaces by magnetic bead microrheometry. Biophys J 75(4):2038–2049. https://doi.org/10.1016/S0006-3495(98)77646-5
Caille N, Thoumine O, Tardy Y, Meister J-J (2002) Contribution of the nucleus to the mechanical properties of endothelial cells. J Biomech 35(2):177–187
Charras GT, Horton MA (2002) Determination of cellular strains by combined atomic force microscopy and finite element modeling. Biophys J 83(2):858–879. https://doi.org/10.1016/S0006-3495(02)75214-4
Collinsworth AM, Torgan CE, Nagda SN, Rajalingam RJ, Kraus WE, Truskey GA (2000) Orientation and length of mammalian skeletal myocytes in response to a unidirectional stretch. Cell Tissue Res 302(2):243–251. https://doi.org/10.1007/s004410000224
Deguchi S, Ohashi T, Sato M (2005) Evaluation of tension in actin bundle of endothelial cells based on preexisting strain and tensile properties measurements. Mol Cell Biomech: MCB 2(3):125–133
Deguchi S, Ohashi T, Sato M (2006) Tensile properties of single stress fibers isolated from cultured vascular smooth muscle cells. J Biomech 39(14.) (January):2603–2610. https://doi.org/10.1016/j.jbiomech.2005.08.026
Deshpande VS, McMeeking RM, Evans AG (2006) A bio-chemo-mechanical model for cell contractility. Proc Natl Acad Sci U S A 103(38):14015–14020. https://doi.org/10.1073/pnas.0605837103
Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689. https://doi.org/10.1016/j.cell.2006.06.044
Gardel ML, Nakamura F, Hartwig JH, Crocker JC, Stossel TP, Weitz DA (2006) Prestressed F-actin networks cross-linked by Hinged Filamins replicate mechanical properties of cells. Proc Natl Acad Sci U S A 103(6):1762–1767. https://doi.org/10.1073/pnas.0504777103
Geiger B, Bershadsky A (2002) Exploring the neighborhood: adhesion-coupled cell mechanosensors. Cell 110(2):139–142
Hao J, Zhang Y, Jing D, Shen Y, Tang G, Huang S, Zhao Z (2015) Mechanobiology of mesenchymal stem cells: perspective into mechanical induction of MSC fate. Acta Biomater 20:1–9. https://doi.org/10.1016/j.actbio.2015.04.008
Heidemann SR, Wirtz D (2004) Towards a regional approach to cell mechanics. Trends Cell Biol 14(4):160–166. https://doi.org/10.1016/j.tcb.2004.02.003
Huang H, Kamm RD, Lee Ri T (2004) Cell mechanics and mechanotransduction: pathways, probes, and physiology. Am J Phys Cell Phys 287(1):C1–C11. https://doi.org/10.1152/ajpcell.00559.2003.
Ingber DE (1993) Cellular tensegrity: defining new rules of biological design that govern the cytoskeleton. J Cell Sci 104(Pt 3):613–627
Ingber DE (2003) Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci 116(7):1157–1173. https://doi.org/10.1242/jcs.00359
Janmey PA (1998) The cytoskeleton and cell signaling: component localization and mechanical coupling. Physiol Rev 78(3):763–781
Janmey PA, Weitz DA (2004) Dealing with mechanics: mechanisms of force transduction in cells. Trends Biochem Sci 29(7):364–370. https://doi.org/10.1016/j.tibs.2004.05.003
Karcher H, Lammerding J, Huang H, Lee RT, Kamm RD, Kaazempur-Mofrad MR (2003) A three-dimensional viscoelastic model for cell deformation with experimental verification. Biophys J 85(5):3336–3349. https://doi.org/10.1016/S0006-3495(03)74753-5
Kardas D, Nackenhorst U, Balzani D (2012) Computational model for the cell-mechanical response of the osteocyte cytoskeleton based on self-stabilizing tensegrity structures. Biomech Model Mechanobiol. https://doi.org/10.1007/s10237-012-0390-y
Kasas S, Wang X, Hirling H, Marsault R, Huni B, Yersin A, Regazzi R et al (2005) Superficial and deep changes of cellular mechanical properties following cytoskeleton disassembly. Cell Motil Cytoskeleton 62(2):124–132. https://doi.org/10.1002/cm.20086
Kasza KE, Rowat AC, Liu J, Angelini TE, Brangwynne CP, Koenderink GH, Weitz DA (2007) The cell as a material. Curr Opin Cell Biol 19(1):101–107. https://doi.org/10.1016/j.ceb.2006.12.002
Kaunas R, Hsu H-J (2009) A kinematic model of stretch-induced stress fiber turnover and reorideshentation. J Theor Biol 257:320–330
Kaunas R, Usami S, Chien S (2006) Regulation of stretch-induced JNK activation by stress fiber orientation. Cell Signal 18:1924–1931
Khetan S, Guvendiren M, Legant WR, Cohen DM, Chen CS, Burdick JA (2013) Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat Mater 12(5):458–465. https://doi.org/10.1038/nmat3586
Kumar S, Maxwell IZ, Heisterkamp A, Polte TR, Lele TP, Salanga M, Mazur E, Ingber DE (2006) Viscoelastic retraction of single living stress fibers and its impact on cell shape, cytoskeletal organization, and extracellular matrix mechanics. Biophys J 90(10):3762–3773. https://doi.org/10.1529/biophysj.105.071506
Kurpinski K, Chu J, Hashi C, Li S (2006) Anisotropic mechanosensing by mesenchymal stem cells. Proc Natl Acad Sci U S A 103(44):16095–16100. https://doi.org/10.1073/pnas.0604182103
Lang T, Wacker I, Wunderlich I, Rohrbach A, Giese G, Soldati T, Almers W (2000) Role of actin cortex in the subplasmalemmal transport of secretory granules in PC-12 cells. Biophys J 78(6):2863–2877. https://doi.org/10.1016/S0006-3495(00)76828-7
Legant WR, Miller JS, Blakely BL, Cohen DM, Genin GM, Chen CS (2010) Measurement of mechanical tractions exerted by cells in three-dimensional matrices. Nat Methods 7(12). https://doi.org/10.1038/nmeth.1531
Legant WR, Choi CK, Miller JS, Shao L, Gao L, Betzig E, Chen CS (2013) Multidimensional traction force microscopy reveals out-of-plane rotational moments about focal adhesions. Proc Natl Acad Sci 110(3):881–886. https://doi.org/10.1073/pnas.1207997110
Lemmon CA, Chen CS, Romer LH (2009) Cell traction forces direct fibronectin matrix assembly. Biophys J 96(2):729–738. https://doi.org/10.1016/j.bpj.2008.10.009
Maniotis AJ, Chen CS, Ingber DE (1997) Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci U S A 94(3):849–854
McCoy RJ, Jungreuthmayer C, O’Brien FJ (2012) Influence of flow rate and scaffold pore size on cell behavior during mechanical stimulation in a flow perfusion bioreactor. Biotechnol Bioeng 109(6):1583–1594. https://doi.org/10.1002/bit.24424
McGarry JG, Prendergast PJ (2004) A three-dimensional finite element model of an adherent eukaryotic cell. Eur Cell Mater 7:27–33; discussion 33–4
McGarry JP, Klein-Nulend J, Mullender MG, Prendergast PJ (2005a) A comparison of strain and fluid shear stress in stimulating bone cell responses – a computational and experimental study. FASEB J: Off Publ Fed Am Soc Exp Biol 19(3):482–484. https://doi.org/10.1096/fj.04-2210fje
Mcgarry JG, Murphy B, Mchugh P (2005b) Computational mechanics modelling of cell–substrate contact during cyclic substrate deformation. J Mech Phys Solids 53(12):2597–2637. https://doi.org/10.1016/j.jmps.2005.07.006
McGarry JP, Fu J, Yang MT, Chen CS, McMeeking RM, Evans AG, Deshpande VS (2009) Simulation of the contractile response of cells on an array of micro-posts. Philos Transact A Math Phys Eng Sci 367(1902):3477–3497. https://doi.org/10.1098/rsta.2009.0097
Mijailovich SM, Kojic M, Zivkovic M, Fabry B, Fredberg JJ (2002) A finite element model of cell deformation during magnetic bead twisting. J Appl Physiol 93:1429–1436. https://doi.org/10.1152/japplphysiol.00255.2002
Mullen CA, Vaughan TJ, Billiar KL, McNarama LM (2015) The effect of substrate stiffness, thickness, and cross-linking density on osteogenic cell behavior. Biophys J 108(7):1604–1612
Nawaz S, Sánchez P, Bodensiek K, Li S, Simons M, Schaap IAT (2012) Cell visco-elasticity measured with AFM and optical trapping at sub-micrometer deformations. Aegerter CM (ed). PLoS One 7(9): e45297. https://doi.org/10.1371/journal.pone.0045297.
Ohayon J, Tracqui P (2005) Computation of adherent cell elasticity for critical cell-bead geometry in magnetic twisting experiments. Ann Biomed Eng 33(2):131–141. https://doi.org/10.1007/s10439-0058972-9.
Pampaloni F, Reynaud EG, Stelzer EHK (2007) The third dimension bridges the gap between cell culture and live tissue. Nat Rev Mol Cell Biol 8:839–845
Pelham RJ, Wang YL (1999) High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate. Mol Biol Cell 10(4):935–945
Pelissier FA, Garbe JC, Ananthanarayanan B, Miyano M, Lin CH, Jokela T, Kumar S, Stampfer MR, Lorens JB, LaBarge MA (2014) Age-related dysfunction in mechanotransduction impairs differentiation of human mammary epithelial progenitors. Cell Rep 7(6):1926–1939. https://doi.org/10.1016/j.celrep.2014.05.021
Rehfeldt F, Discher DE (2007) Cell dipoles feel their way quantum to classical and back. Nat Phys 3:592–593
Reynolds NH, Ronan W, Dowling EP, Owens P, McMeeking RM, McGarry JP (2014) On the role of the actin cytoskeleton and nucleus in the biomechanical response of spread cells. Biomaterials 35(13):4015–4025
Ronan W, Deshpande VS, McMeeking RM, McGarry JP (2012) Numerical investigation of the active role of the actin cytoskeleton in the compression resistance of cells. J Mech Behav Biomed Mater 14:143–157. https://doi.org/10.1016/j.jmbbm.2012.05.016
Schaap IAT, Carrasco C, de Pablo PJ, MacKintosh FC, Schmidt CF (2006) Elastic response, buckling, and instability of microtubules under radial indentation. Biophys J 91(4):1521–1531. https://doi.org/10.1529/biophysj.105.077826
Stamenović D, Coughlin MF (1999) The role of prestress and architecture of the cytoskeleton and deformability of cytoskeletal filaments in mechanics of adherent cells: a quantitative analysis. J Theor Biol 201(1):63–74. https://doi.org/10.1006/jtbi.1999.1014
Stamenović D, Mijailovich SM, Tolić-Nørrelykke IM, Chen J, Wang N (2002) Cell prestress. II. Contribution of microtubules. Am J Phys Cell Phys 282(3):C617–C624. https://doi.org/10.1152/ajpcell.00271.2001
Tapley EC, Starr DA (2013) Connecting the nucleus to the cytoskeleton by SUN-KASH bridges across the nuclear envelope. Curr Opin Cell Biol 25(1):57–62. https://doi.org/10.1016/j.ceb.2012.10.014
Unnikrishnan GU, Unnikrishnan VU, Reddy JN (2007) Constitutive material modeling of cell: a micromechanics approach. J Biomech Eng 129(3):315–323. https://doi.org/10.1115/1.2720908.
Van Citters KM, Hoffman BD, Massiera G, Crocker JC (2006) The role of F-actin and myosin in epithelial cell rheology. Biophys J 91(10):3946–3956. https://doi.org/10.1529/biophysj.106.091264
Wang N (1998) Mechanical interactions among cytoskeletal filaments. Hypertension 32(1):162–165
Wang N, Ingber D (1994) Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. Biophys J 66(6):2181–2189. https://doi.org/10.1016/S0006-3495(94)81014-8
Wang JH, Goldschmidt-Clermont P, Wille J, Yin FC (2001) Specificity of endothelial cell reorientation in response to cyclic mechanical stretching. J Biomech 34(12):1563–1572
Wang N, Tolić-Nørrelykke IM, Chen J, Mijailovich SM, Butler JP, Fredberg JJ, Stamenović D (2002) Cell prestress. I. Stiffness and prestress are closely associated in adherent contractile cells. Am J Phys Cell Phys 282(3):C606–C616. https://doi.org/10.1152/ajpcell.00269.2001
Wang N, Tytell JD, Ingber DE (2009) Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 10(1):75–82. https://doi.org/10.1038/nrm2594
Weafer PP, Ronan W, Jarvi SP s, McGarry JP (2013) Experimental and computational investigation of the role of stress fiber contractility in the resistance of osteoblasts to compression. Bull Math Biol 75(8):1284–1303. https://doi.org/10.1007/s11538-013-9812-y.
Wozniak MA, Chen CS (2009) Mechanotransduction in development: a growing role for contractility. Nat Rev Mol Cell Biol 10(1):34–43. https://doi.org/10.1038/nrm2592
Xu W, Mezencev R, Kim B, Wang L, McDonald J, Sulchek T (2012) Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells. PLoS One 7(10):e46609. https://doi.org/10.1371/journal.pone.0046609
Zemel A, Safran S (2007) Active self-polarization of contractile cells in asymmetrically shaped domains. Phys Rev E Stat Nonlinear Soft Matter Phys 76(2 Pt 1):021905. https://doi.org/10.1103/PhysRevE.76.021905
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Barreto, S., Lacroix, D. (2019). Mechanical Load Transfer at the Cellular Level. In: Multiscale Mechanobiology in Tissue Engineering. Frontiers of Biomechanics, vol 3. Springer, Singapore. https://doi.org/10.1007/978-981-10-8075-3_9
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