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Biomechanics and Modeling in Mechanobiology

, Volume 15, Issue 6, pp 1495–1508 | Cite as

Effects of oxidative stress-induced changes in the actin cytoskeletal structure on myoblast damage under compressive stress: confocal-based cell-specific finite element analysis

  • Yifei Yao
  • Damien Lacroix
  • Arthur F. T. Mak
Original Paper

Abstract

Muscle cells are frequently subjected to both mechanical and oxidative stresses in various physiological and pathological situations. To explore the mechanical mechanism of muscle cell damage under loading and oxidative stresses, we experimentally studied the effects of extrinsic hydrogen peroxides on the actin cytoskeletal structure in C2C12 myoblasts and presented a finite element (FE) analysis of how such changes in the actin cytoskeletal structure affected a myoblast’s capability to resist damage under compression. A confocal-based cell-specific FE model was built to parametrically study the effects of stress fiber density, fiber cross-sectional area, fiber tensile prestrain, as well as the elastic moduli of the stress fibers, actin cortex, nucleus and cytoplasm. The results showed that a decrease in the elastic moduli of both the stress fibers and actin cortex could increase the average tensile strain on the actin cortex–membrane structure and reduce the apparent cell elastic modulus. Assuming the cell would die when a certain percentage of membrane elements were strained beyond a threshold, a lower elastic modulus of actin cytoskeleton would compromise the compressive resistance of a myoblast and lead to cell death more readily. This model was used with a Weibull distribution function to successfully describe the extent of myoblasts damaged in a monolayer under compression.

Keywords

Oxidative stress Actin cytoskeleton Myoblast  Finite element modeling Weibull distribution 

Notes

Acknowledgments

This study was supported by Hong Kong Research Grant Council (RGC Ref. No. CUHK415413). And we thank Mr. Chan Jiajie for facilitating the operation of confocal microscope.

Compliance with ethical standards

Conflict of interest

No conflict of interest.

References

  1. Barreto S, Clausen CH, Perrault CM, Fletcher DA, Lacroix D (2013) A multi-structural single cell model of force-induced interactions of cytoskeletal components. Biomaterials 34(26):6119–6126CrossRefGoogle Scholar
  2. Barreto S, Perrault CM, Lacroix D (2014) Structural finite element analysis to explain cell mechanics variability. J Mech Behav Biomed Mater 38:219–231CrossRefGoogle Scholar
  3. Bausch AR, Möller W, Sackmann E (1999) Measurement of local viscoelasticity and forces in living cells by magnetic tweezers. Biophys J 76(1):573–579CrossRefGoogle Scholar
  4. Blanchoin L, Boujemaa-Paterski R, Sykes C, Plastino J (2014) Actin dynamics, architecture, and mechanics in cell motility. Physiol Rev 94(1):235–263CrossRefGoogle Scholar
  5. Caille N, Thoumine O, Tardy Y, Meister J (2002) Contribution of the nucleus to the mechanical properties of endothelial cells. J Biomech 35(2):177–187CrossRefGoogle Scholar
  6. Canović EP, Seidl DT, Polio SR, Oberai AA, Barbone PE, Stamenović D, Smith ML (2014) Biomechanical imaging of cell stiffness and prestress with subcellular resolution. Biomech Model Mechanobiol 13(3):665–678CrossRefGoogle Scholar
  7. Collinsworth AM, Zhang S, Kraus WE, Truskey GA (2002) Apparent elastic modulus and hysteresis of skeletal muscle cells throughout differentiation. Am J Physiol Cell Physiol 283(4):C1219–C1227CrossRefGoogle Scholar
  8. 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 2(3):125Google Scholar
  9. Duan X, Chan KT, Lee KKH, Mak AFT (2015) Oxidative stress and plasma membrane repair in single myoblasts after femtosecond laser photoporation. Ann Biomed Eng 43(11):2735–2744CrossRefGoogle Scholar
  10. Fletcher DA, Mullins RD (2010) Cell mechanics and the cytoskeleton. Nature 463(7280):485–492CrossRefGoogle Scholar
  11. Gavara N, Chadwick RS (2015) Relationship between cell stiffness and stress fiber amount, assessed by simultaneous atomic force microscopy and live-cell fluorescence imaging. Biomech Model Mechanobiol 1–13Google Scholar
  12. Griffin MA, Sen S, Sweeney HL, Discher DE (2004) Adhesion-contractile balance in myocyte differentiation. J Cell Sci 117(24):5855–5863CrossRefGoogle Scholar
  13. Guilak F, Tedrow JR, Burgkart R (2000) Viscoelastic properties of the cell nucleus. Biochem Biophys Res Commun 269(3):781–786CrossRefGoogle Scholar
  14. Huot J, Houle F, Marceau F, Landry J (1997) Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase/heat shock protein 27 pathway in vascular endothelial cells. Circ Res 80(3):383–392CrossRefGoogle Scholar
  15. Janmey PA, McCulloch CA (2007) Cell mechanics: integrating cell responses to mechanical stimuli. Annu Rev Biomed Eng 9:1–34CrossRefGoogle Scholar
  16. Knight MM, Toyoda T, Lee DA, Bader DL (2006) Mechanical compression and hydrostatic pressure induce reversible changes in actin cytoskeletal organisation in chondrocytes in agarose. J Biomech 39(8):1547–1551CrossRefGoogle Scholar
  17. Kreis TE, Birchmeier W (1980) Stress fiber sarcomeres of fibroblasts are contractile. Cell 22(2):555–561CrossRefGoogle Scholar
  18. Leccia E, Batonnet-Pichon S, Tarze A, Bailleux V, Doucet J, Pelloux M, Delort F, Pizon V, Vicart P, Briki F (2013) Cyclic stretch reveals a mechanical role for intermediate filaments in a desminopathic cell model. Phys Biol 10(1):016001CrossRefGoogle Scholar
  19. Liu L, Yuan W, Wang J (2010) Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress. Biomech Model Mechanobiol 9(6):659–670CrossRefGoogle Scholar
  20. Lu L, Feng Y, Hucker WJ, Oswald SJ, Longmore GD, Yin FCP (2008a) Actin stress fiber pre-extension in human aortic endothelial cells. Cell Cotil Cytoskelet 65(4):281–294CrossRefGoogle Scholar
  21. Lu L, Oswald SJ, Ngu H, Yin FCP (2008b) Mechanical properties of actin stress fibers in living cells. Biophys J 95(12):6060–6071CrossRefGoogle Scholar
  22. Ma Z, Wu YS, Mak AFT (2015) Rheological behavior of actin stress fibers in myoblasts after nanodissection: effects of oxidative stress. Biorheology 1–10 (Preprint)Google Scholar
  23. Matés JM, Segura JA, Alonso FJ, Márquez J (2008) Intracellular redox status and oxidative stress: implications for cell proliferation, apoptosis, and carcinogenesis. Arch Toxicol 82(5):273–299CrossRefGoogle Scholar
  24. Neisch AL, Fehon RG (2011) Ezrin, radixin and moesin: key regulators of membrane–cortex interactions and signaling. Curr Opin Cell Biol 23(4):377–382CrossRefGoogle Scholar
  25. Ofek G, Wiltz DC, Athanasiou KA (2009) Contribution of the cytoskeleton to the compressive properties and recovery behavior of single cells. Biophys J 97(7):1873–1882CrossRefGoogle Scholar
  26. Or-Tzadikario S, Gefen A (2011) Confocal-based cell-specific finite element modeling extended to study variable cell shapes and intracellular structures: the example of the adipocyte. J Biomech 44(3):567–573CrossRefGoogle Scholar
  27. Pan NC, Ma JJ, Peng HB (2012) Mechanosensitivity of nicotinic receptors. Pflugers Arch 464(2):193–203CrossRefGoogle Scholar
  28. Peeters EA, Oomens CW, Bouten CV, Bader DL, Baaijens FP (2005a) Viscoelastic properties of single attached cells under compression. J Biomech Eng 127(2):237–243CrossRefGoogle Scholar
  29. Peeters EAG, Oomens CWJ, Bouten CVC, Bader DL, Baaijens FPT (2005b) Mechanical and failure properties of single attached cells under compression. J Biomech 38(8):1685–1693CrossRefGoogle Scholar
  30. Polacheck WJ, German AE, Mammoto A, Ingber DE, Kamm RD (2014) Mechanotransduction of fluid stresses governs 3D cell migration. Proc Natl Acad Sci 111(7):2447–2452CrossRefGoogle Scholar
  31. Rotsch C, Radmacher M (2000) Drug-induced changes of cytoskeletal structure and mechanics in fibroblasts: an atomic force microscopy study. Biophys J 78(1):520–535CrossRefGoogle Scholar
  32. Salbreux G, Charras G, Paluch E (2012) Actin cortex mechanics and cellular morphogenesis. Trends Cell Biol 22(10):536–545CrossRefGoogle Scholar
  33. Sbrana F, Sassoli C, Meacci E, Nosi D, Squecco R, Paternostro F, Tiribilli B, Zecchi-Orlandini S, Francini F, Formigli L (2008) Role for stress fiber contraction in surface tension development and stretch-activated channel regulation in C2C12 myoblasts. Am J Physiol Cell Physiol 295(1):C160–C172CrossRefGoogle Scholar
  34. Sheehy SP, Grosberg A, Parker KK (2012) The contribution of cellular mechanotransduction to cardiomyocyte form and function. Biomech Model Mechanobiol 11(8):1227–1239CrossRefGoogle Scholar
  35. Slomka N, Gefen A (2010) Confocal microscopy-based three-dimensional cell-specific modeling for large deformation analyses in cellular mechanics. J Biomech 43(9):1806–1816CrossRefGoogle Scholar
  36. Slomka N, Gefen A (2011) Cell-to-cell variability in deformations across compressed myoblasts. J Biomech Eng 133(8):081007CrossRefGoogle Scholar
  37. Slomka N, Gefen A (2012) Relationship between strain levels and permeability of the plasma membrane in statically stretched myoblasts. Ann Biomed Eng 40(3):606–618CrossRefGoogle Scholar
  38. Slomka N, Oomens CW, Gefen A (2011) Evaluating the effective shear modulus of the cytoplasm in cultured myoblasts subjected to compression using an inverse finite element method. J Mech Behav Biomed Mater 4(7):1559–1566CrossRefGoogle Scholar
  39. Stricker J, Falzone T, Gardel ML (2010) Mechanics of the F-actin cytoskeleton. J Biomech 43(1):9–14CrossRefGoogle Scholar
  40. Sun S, Wong S, Mak A, Cho M (2014) Impact of oxidative stress on cellular biomechanics and rho signaling in C2C12 myoblasts. J Biomech 47(15):3650–3656CrossRefGoogle Scholar
  41. Wakatsuki T, Schwab B, Thompson NC, Elson EL (2001) Effects of cytochalasin D and latrunculin B on mechanical properties of cells. J Cell Sci 114(5):1025–1036Google Scholar
  42. Wang N, Naruse K, Stamenović D, Fredberg JJ, Mijailovich SM, Tolić-Nørrelykke IM, Polte T, Mannix R, Ingber DE (2001) Mechanical behavior in living cells consistent with the tensegrity model. Proc Natl Acad Sci 98(14):7765–7770CrossRefGoogle Scholar
  43. 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 Physiol Cell Physiol 282(3):C606–C616CrossRefGoogle Scholar
  44. Wang N, Stamenovic D (2000) Contribution of intermediate filaments to cell stiffness, stiffening, and growth. Am J Physiol Cell Physiol 279:188–194Google Scholar
  45. Wirtz D (2009) Particle-tracking microrheology of living cells: principles and applications. Annu Rev Biophys 38:301–326CrossRefGoogle Scholar
  46. Wong SW, Sun S, Cho M, Lee KK, Mak AFT (2015) \({\text{ H }_2}{\text{ O }_2}\) exposure affects myotube stiffness and actin filament polymerization. Ann Biomed Eng 43(5):1178–1188CrossRefGoogle Scholar
  47. Yan YX, Gong YW, Guo Y, Lv Q, Guo C, Zhuang Y, Zhang Y, Li R, Zhang XZ (2012) Mechanical strain regulates osteoblast proliferation through integrin-mediated ERK activation. PloS One 7(4):e35709CrossRefGoogle Scholar
  48. Yao Y, Xiao Z, Wong SW, Hsu Y, Cheng T, Chang C, Bian L, Mak A (2015) The effects of oxidative stress on the compressive damage thresholds of C2C12 mouse myoblasts—implications for deep tissue injury. Ann Biomed Eng 43(2):287–296CrossRefGoogle Scholar
  49. Yim EK, Sheetz MP (2012) Force-dependent cell signaling in stem cell differentiation. Stem Cell Res Ther 3(5):41CrossRefGoogle Scholar
  50. Zhu D, Tan KS, Zhang X, Sun AY, Sun GY, Lee JCM (2005) Hydrogen peroxide alters membrane and cytoskeleton properties and increases intercellular connections in astrocytes. J Cell Sci 118(16):3695–3703CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Yifei Yao
    • 1
    • 2
  • Damien Lacroix
    • 2
  • Arthur F. T. Mak
    • 1
  1. 1.Division of Biomedical EngineeringThe Chinese University of Hong KongShatinChina
  2. 2.Department of Mechanical Engineering, INSIGNEO Institute for In Silico MedicineUniversity of SheffieldSheffieldUK

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