Skip to main content

Advertisement

SpringerLink
Log in

Stress fiber growth and remodeling determines cellular morphomechanics under uniaxial cyclic stretch

  • Original Paper
  • Published:
Biomechanics and Modeling in Mechanobiology Aims and scope Submit manuscript

Abstract

Stress fibers in the cytoskeleton are essential in maintaining cellular shape and influence cellular adhesion and migration. Cyclic uniaxial stretching results in cellular reorientation orthogonal to the applied stretch direction. The mechanistic cues underlying changes to cellular form and function to stretch stimuli are currently underexplored. We show stretch-induced stress fiber lengthening, their realignment, and increased cortical actin in NIH 3T3 fibroblasts stretched over varied amplitudes and durations. Higher amounts of actin and stress fiber alignment were accompanied with an increase in the effective elastic modulus of cells. Microtubules did not contribute to the measured stiffness or reorientation response but were essential to the nuclear reorientation. We used a phenomenological growth and remodeling law, based on the experimental data, to model stress fiber elongation and reorientation dynamics based on a nonlinear, orthotropic, fiber-reinforced continuum representation of the cell. The model predicts the changes observed fibroblast morphology and increased cellular stiffness under uniaxial cyclic stretch which agrees with experimental results. Such studies are important in exploring the differences underlying mechanotransduction and cellular contractility under stretch.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Agrawal V, Kollimada SA, Byju AG, Gundiah N (2013) Regional variations in the nonlinearity and anisotropy of bovine aortic elastin. Biomech Model Mechanobiol 12:1181–1194

    Google Scholar 

  • Balaban NQ, Schwarz US, Riveline D, Goichberg P, Tzur G, Sabanay I, Mahalu D, Safran S, Bershadsky A, Addadi L, Geiger B (2001) Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat Cell Biol 3(5):466–472

    Google Scholar 

  • 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):6119–6126

    Google Scholar 

  • Bauër P, Tavacoli J, Pujol T, Planade J, Heuvingh J, Du Roure O (2017) A new method to measure mechanics and dynamic assembly of branched actin networks. Sci Rep 1:15688

    Google Scholar 

  • Buck RC (1980) Reorientation response of cells to repeated stretch and recoil of the substratum. Exp Cell Res 127(2):470–474

    MathSciNet  Google Scholar 

  • Chen B, Kemkemer R, Deibler M, Spatz J, Gao H (2012) Cyclic stretch induces cell reorientation on substrates by destabilizing catch bonds in focal adhesions. PLoS ONE 7(11):48346

    Google Scholar 

  • Chen Y, Pasapera AM, Koretsky AP, Waterman CM (2013) Orientation-specific responses to sustained uniaxial stretching in focal adhesion growth and turnover. Proc Natl Acad Sci USA 110(26):E2352–E2361

    Google Scholar 

  • Chen K, Vigliotti A, Bacca M, McMeeking RM, Deshpande VS, Holmes JW (2018) Role of boundary conditions in determining cell alignment in response to stretch. Proc Natl Acad Sci USA 115(5):986–991

    Google Scholar 

  • Cirka H, Monterosso M, Diamantides N, Favreau J, Wen Q, Billiar K (2016) Active traction force response to long-term cyclic stretch is dependent on cell pre-stress. Biophys J 110(8):1845–1857

    Google Scholar 

  • Clark AG, Dierkes K, Paluch EK (2013) Monitoring actin cortex thickness in live cells. Biophys J 105:570–580. https://doi.org/10.1016/j.bpj.2013.05.057

    Article  Google Scholar 

  • Cui Y, Hameed MF, Yang B, Lee K, Pan CQ, Park S, Sheetz M (2015) Cyclic stretching of soft substrates induces spreading and growth. Nat Commun 6(1):6333

    Google Scholar 

  • Darling EM, Zauscher S, Block JA, Guilak FA (2007) Thin-layer model for viscoelastic, stress-relaxation testing of cells using atomic force microscopy: Do cell properties reflect metastatic potential? Biophys J 92(5):1784–1791

    Google Scholar 

  • De R, Zemel A, Safran SA (2007) Dynamics of cell orientation. Nat Phys 3(9):655–659

    Google Scholar 

  • Dimitriadis EK, Horkay F, Maresca J, Kachar B, Chadwick RS (2002) Determination of elastic moduli of thin layers of soft material using the atomic force microscope. Biophys J 82(5):2798–2810

    Google Scholar 

  • Efremov YM, Velay-Lizancos M, Weaver CJ, Athamneh AI, Zavattieri PD, Suter DM, Raman A (2019) Anisotropy vs isotropy in living cell indentation with AFM. Sci Rep 9:5757

    Google Scholar 

  • Foolen J, Marloes WJT, Broek JVD, Baaijens F (2014) Synergy between Rho signaling and matrix density in cyclic stretch-induced stress fiber organization. Acta Biomater 10:1876–1885

    Google Scholar 

  • Gavara N, Chadwick RS (2016) Relationship between cell stiffness and stress fiber amount, assessed by simultaneous atomic force microscopy and live-cell fluorescence imaging. Biomech Model Mechanobiol 15(3):511–523

    Google Scholar 

  • Göktepe S, Abilez OJ, Parker KK, Kuhl E (2010) A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis. J Theor Biol 265(3):433–442

    MATH  Google Scholar 

  • Goldyn AM, Rioja BA, Spatz JP, Ballestrem C, Kemkemer R (2009) Force-induced cell polarisation is linked to RhoA-driven microtubule-independent focal-adhesion sliding. J Cell Sci 122(20):3644–3651

    Google Scholar 

  • Goldyn AM, Kaiser P, Spatz JP, Ballestrem C, Kemkemer R (2010) The kinetics of force-induced cell reorganization depend on microtubules and actin. Cytoskeleton 67:241–250

    Google Scholar 

  • Goriely A (2017) The Mathematics and mechanics of biological growth. Springer, New York. https://doi.org/10.1007/978-0-387-87710-5

    Book  MATH  Google Scholar 

  • Greiner AM, Chen H, Spatz JP, Kemkemer R (2013) Cyclic tensile strain controls cell shape and directs actin stress fiber formation and focal adhesion alignment in spreading cells. PLoS ONE. https://doi.org/10.1371/journal.pone.0077328

    Article  Google Scholar 

  • Gundiah N, Ratcliffe MB, Pruitt LA (2009) The biomechanics of arterial elastin. J Mech Behav Biomed Mater 2(3):288–296

    Google Scholar 

  • Haase K, Pelling AE (2013) The role of the actin cortex in maintaining cell shape. Commun Integr Biol 6(6):e26714

    Google Scholar 

  • Hayakawa K, Sato N, Obinata T (2001) Dynamic reorientation of cultured cells and stress fibers under mechanical stress from periodic stretching. Exp Cell Res 268(1):104–114

    Google Scholar 

  • Hoffman L, Jensen CC, Yoshigi M, Beckerle M (2017) Mechanical signals activate p38 MAPK pathway-dependent reinforcement of actin via mechanosensitive HspB1. Mol Biol Cell 28(20):2661–2675

    Google Scholar 

  • Hough PVC (1962) Method and means for recognizing complex patterns. US Patent 3,069,654

  • Hsu HJ, Lee CF, Locke A, Vanderzyl SQ, Kaunas R (2010) Stretch-induced stress fiber remodeling and the activations of JNK and ERK depend on mechanical strain rate, but not FAK. PLoS ONE 5(8):e12470

    Google Scholar 

  • Huang W, Matsui ST, Saito T, Kuragano M, Takahashi M, Kawahara T, Sato M, Deguchi S (2021) Mechanosensitive myosin II but not cofilin primarily contributes to cyclic cell stretch-induced selective disassembly of actin stress fibers. Am J Physiol Cell Physiol 320:C1153–C1163

    Google Scholar 

  • Humphrey JD, Rajagopal KR (2002) A constrained mixture model for growth and remodeling of soft tissues. Math Model Methods Appl Sci 12(03):407–430

    MathSciNet  MATH  Google Scholar 

  • Imatani S, Maugin GA (2002) Constitutive model for material growth and its application to three-dimensional finite element analysis. Mech Res Commun 29(6):477–483

    MathSciNet  MATH  Google Scholar 

  • Jungbauer S, Gao H, Spatz JP, Kemkemer R (2008) Two characteristic regimes in frequency-dependent dynamic reorientation of fibroblasts on cyclically stretched substrates. Biophys J 95(7):3470–3478

    Google Scholar 

  • Kaunas R, Nguyen P, Usami S, Chien S (2005) Cooperative effects of Rho and mechanical stretch on stress fiber organization. Proc Natl Acad Sci USA 102(44):15895–15900

    Google Scholar 

  • Kaunas R, Hsu HJ, Deguchi S (2010) Sarcomeric model of stretch-induced stress fiber reorganization. Cell Health Cytoskelet 3:13

    Google Scholar 

  • Kolodney MS, Elson EL (1995) Contraction due to microtubule disruption is associated with increased phosphorylation of myosin regulatory light chain. Proc Natl Acad Sci USA 92:10252–10256

    Google Scholar 

  • Kulkarni AH, Chatterjee A, Kondaiah P, Gundiah N (2018) TGF-β induces changes in breast cancer cell deformability. Phys Biol 15(6):065005

    Google Scholar 

  • 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 10:016001

    Google Scholar 

  • Lien JC, Wang YL (2021) Cyclic stretching-induced epithelial cell reorientation is driven by microtubule-modulated transverse extension during the relaxation phase. Sci Rep 11:14803

    Google Scholar 

  • Livne A, Geiger B (2016) The inner workings of stress fibers—from contractile machinery to focal adhesions and back. J Cell Sci 129(7):1293–1304

    Google Scholar 

  • Livne A, Bouchbinder E, Geiger B (2014) Cell reorientation under cyclic stretching. Nat Commun 5:1–8

    Google Scholar 

  • Melnik AV, Goriely A (2013) Dynamic fiber reorientation in a fiber-reinforced hyperelastic material. Math Mech Solids 18(6):634–648

    MathSciNet  MATH  Google Scholar 

  • Menzel A (2005) Modelling of anisotropic growth in biological tissues. Biomech Model Mechanobiol 3(3):147–171

    Google Scholar 

  • Merodio J, Ogden RW (2002) Material instabilities in fiber-reinforced nonlinearly elastic solids under plane deformation. Arch Mech 54(5–6):525–552

    MathSciNet  MATH  Google Scholar 

  • Morioka M, Parameswaran H, Naruse K, Kondo M, Sokabez M, Hesegawa Y, Suki B, Ito S (2011) Microtubule dynamics regulate cyclic stretch-induced cell alignment in human airway smooth muscle cells. PLoS ONE 6(10):e26384

    Google Scholar 

  • Nekouzadeh A, Pryse KM, Elson EL, Genin GM (2008) Stretch-activated force shedding, force recovery, and cytoskeletal remodeling in contractile fibroblasts. J Biomech 41(14):2964–2971

    Google Scholar 

  • Parekh SH, Chaudhuri O, Theriot JA, Fletcher DA (2005) Loading history determines the velocity of actin-network growth. Nat Cell Biol 7(12):1119–1123

    Google Scholar 

  • Pender N, McCulloch CA (1991) Quantitation of actin polymerization in two human fibroblast sub-types responding to mechanical stretching. J Cell Sci 100:187–193

    Google Scholar 

  • Perrault CM, Brugues A, Bazellieres E, Pierre Ricco P, Lacroix D, Trepat X (2015) Traction forces of endothelial cells under slow shear flow. Biophys J 109(8):1533–1536

    Google Scholar 

  • Robertson AM, Watton PN (2013) Mechanobiology of the arterial wall. Transp Biol Media, pp 275–347

  • Rodriguez EK, Hoger A, McCulloch AD (1994) Stress-dependent finite growth in soft elastic tissues. J Biomech 27(4):455–467

    Google Scholar 

  • Sakamoto Y, Buchanan RM, Sanchez-Adams J, Guilak F, Sacks MS (2017) On the functional role of valve interstitial cell stress fibers: a continuum modeling approach. J Biomech Eng 139:021007

    Google Scholar 

  • Salbreux G, Charras G, Paluch E (2012) Actin cortex mechanics and cellular morphogenesis. Trends Cell Biol 22:536–545

    Google Scholar 

  • Schriefl AJ, Reinisch AJ, Sankaran S, Pierce DM, Holzapfel GA (2013) Quantitative assessment of collagen fibre orientations from two-dimensional images of soft biological tissues. J R Soc Interface 9(76):3081–3093

    Google Scholar 

  • Thompson DW (1917) On growth and form. Cambridge University Press, Cambridge

    Google Scholar 

  • Tjorve E, Tjorve MCK (2010) A unified approach to the Richards-model family for use in growth analyses: why we need only two model forms. J TheoR Biol 2010(267):417–425

    MathSciNet  MATH  Google Scholar 

  • Wang N, Stamenovic D (2000) Contribution of intermediate filaments to cell stiffness, stiffening, and growth. Am J Physiol Cell Physiol 279:188–194

    Google Scholar 

  • Wang JHC, Goldschmidt CP, Wille J, Yin FCP (2001) Specificity of endothelial cell reorientation in response to cyclic mechanical stretching. J Biomech 34(12):1563–1572

    Google Scholar 

  • Zielinski A, Linnartz C, Pleschka C, Dreissen G, Springer R, Merkel R, Hoffmann B (2018) Reorientation dynamics and structural interdependencies of actin, microtubules and intermediate filaments upon cyclic stretch application. Cytoskeleton 75:385–394

    Google Scholar 

Preprint

  • Chatterjee A, Kondaiah P, Gundiah N, (2019) Stress fiber growth and remodeling determines cellular morphomechanics under uniaxial cyclic stretch, bioRxiv: https://doi.org/10.1101/622092v1. preprint posted 29 April, 2019

Download references

Acknowledgements

We thank Ms. Monisha Mohandas (BSSE, IISc) for help with the AFM. We also thank Ms. Dhulika Ravinuthala who helped in performing some of the uniaxial cyclic stretch experiments reported in this study. NG gratefully acknowledges the Department of Biotechnology (BBI2) and Department of Science and Technology (SERB/003640) for project support. PK laboratory is supported by IISc-DBT partnership program and DST-FIST infrastructure to MRDG.

Author information

Authors and Affiliations

  1. Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, Karnataka, 560012, India

    Aritra Chatterjee & Namrata Gundiah

  2. Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, 560012, India

    Paturu Kondaiah

  3. Department of Mechanical Engineering, Indian Institute of Science, Bangalore, Karnataka, 560012, India

    Namrata Gundiah

Authors
  1. Aritra Chatterjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paturu Kondaiah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Namrata Gundiah
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

AC performed the experiments, analyzed the data, completed the theoretical model, and helped write the manuscript. PK provided inputs on the data interpretation and results. NG designed the study, supervised the research, helped with data analysis, and wrote the manuscript with inputs from all authors.

Corresponding author

Correspondence to Namrata Gundiah.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1249 kb)

Supplementary file2 (MOV 7303 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chatterjee, A., Kondaiah, P. & Gundiah, N. Stress fiber growth and remodeling determines cellular morphomechanics under uniaxial cyclic stretch. Biomech Model Mechanobiol 21, 553–567 (2022). https://doi.org/10.1007/s10237-021-01548-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10237-021-01548-z

Keywords

Search

Navigation