Abstract
Shear stress plays a crucial role in many physiological processes, such as atherosclerosis, angiogenesis, and metastasis. However, how cells respond to static and dynamical shear stresses remains poorly understood. Here, we propose a structure-based cellular model, consisting of cell membrane, cytoplasm, and cytoskeleton, to explore the shear rheology of cells. By simulating the mechanical responses of a single cell under shear stress, we find that this model can reproduce both the universal power-law rheology at small deformations and stress stiffening at large deformations. Besides, the loss moduli of cells at high frequencies exhibit a stronger frequency dependence than the storage moduli. Moreover, we present two master relations: one is between the power-law exponent and cell stiffness; the other is between cell stiffness and external forces. Our results are in broad agreement with experiments. The self-similar hierarchical theory offers a physical explanation of the power-law responses of cells under shear stress. In addition, we consider the geometrical nonlinearity of single filaments to account for the stress stiffening of cells. The present model can be used to examine the effects of shear flow on living cells in physiological environments.
摘要
剪应力在许多生理过程中都起着至关重要的作用, 例如动脉粥样硬化、血管生成和肿瘤转移等. 然而, 细胞对静态和动态剪应 力的响应仍然知之甚少. 考虑细胞膜、细胞质和细胞骨架等结构特征, 本文提出了一个基于结构的细胞模型以探究细胞的剪切流变学. 通过模拟单个细胞在剪应力下的力学响应, 我们发现该模型可以再现细胞小变形时的幂律流变学和大变形时的应力硬化特性. 此外, 细胞在高频下的损耗模量表现出比存储模量更强的频率依赖性. 进而, 我们提出了两个重要关系: 一个是幂律指数和细胞刚度之间的 关系; 另一个是在细胞刚度和外力之间的关系. 我们的预测结果与很多实验结果一致. 自相似多级理论为细胞在剪应力下的幂律响应 提供了物理解释. 此外, 我们考虑了单根纤维的几何非线性, 以便解释细胞的应力硬化. 本模型可用于研究剪切流动对生理环境下活细 胞的影响.
References
E. P. Dowling, W. Ronan, G. Ofek, V. S. Deshpande, R. M. McMeeking, K. A. Athanasiou, and J. P. McGarry, The effect of remodelling and contractility of the actin cytoskeleton on the shear resistance of single cells: A computational and experimental investigation, J. R. Soc. Interface. 9, 3469 (2012).
C. Souilhol, J. Serbanovic-Canic, M. Fragiadaki, T. J. Chico, V. Rid-ger, H. Roddie, and P. C. Evans, Endothelial responses to shear stress in atherosclerosis: a novel role for developmental genes, Nat. Rev. Cardiol. 17, 52 (2020).
D. A. Fletcher, and R. D. Mullins, Cell mechanics and the cytoskeleton, Nature 463, 485 (2010).
P. Lappalainen, T. Kotila, A. Jégou, and G. Romet-Lemonne, Biochemical and mechanical regulation of actin dynamics, Nat. Rev. Mol. Cell. Biol. 23, 836 (2022).
N. Desprat, A. Richert, J. Simeon, and A. Asnacios, Creep function of a single living cell, Biophys. J. 88, 2224 (2005).
P. Kollmannsberger, C. T. Mierke, and B. Fabry, Nonlinear viscoe-lasticity of adherent cells is controlled by cytoskeletal tension, Soft Matter 7, 3127 (2011).
P. Fernández1, L. Heymann, A. Ott, N. Aksel, and P. A. Pullarkat, Shear rheology of a cell monolayer, New. J. Phys. 9, 419 (2007).
B. Fabry, G. N. Maksym, J. P. Butler, M. Glogauer, D. Navajas, and J. J. Fredberg, Scaling the microrheology of living cells, Phys. Rev. Lett. 87, 148102 (2001).
B. D. Hoffman, G. Massiera, K. M. van Citters, and J. C. Crocker, The consensus mechanics of cultured mammalian cells, Proc. Natl. Acad. Sci. USA 103, 10259 (2006).
A. Rigato, A. Miyagi, S. Scheuring, and F. Rico, High-frequency microrheology reveals cytoskeleton dynamics in living cells, Nat. Phys. 13, 771 (2017).
M. Balland, N. Desprat, D. Icard, S. Féréol, A. Asnacios, J. Bro-waeys, S. Hénon, and F. Gallet, Power laws in microrheology experiments on living cells: Comparative analysis and modeling, Phys. Rev. E 74, 021911 (2006).
P. Kollmannsberger, and B. Fabry, Linear and nonlinear rheology of living cells, Annu. Rev. Mater. Res. 41, 75 (2011).
L. Deng, X. Trepat, J. P. Butler, E. Millet, K. G. Morgan, D. A. Weitz, and J. J. Fredberg, Fast and slow dynamics of the cytoskeleton, Nat. Mater 5, 636 (2006).
G. H. Koenderink, M. Atakhorrami, F. C. Mackintosh, and C. F. Schmidt, High-frequency stress relaxation in semiflexible polymer solutions and networks, Phys. Rev. Lett. 96, 138307 (2006).
P. Fernández, P. A. Pullarkat, and A. Ott, A master relation defines the nonlinear viscoelasticity of single fibroblasts, Biophys. J. 90, 3796 (2006).
M. Sander, H. Dobicki, and A. Ott, Large amplitude oscillatory shear rheology of living fibroblasts: Path-dependent steady states, Biophys. J. 113, 1561 (2017).
S. Wendling, C. Oddou, and D. Isabey, Stiffening response of a cellular tensegrity model, J. Theor. Biol. 196, 309 (1999).
C. Semmrich, T. Storz, J. Glaser, R. Merkel, A. R. Bausch, and K. Kroy, Glass transition and rheological redundancy in F-actin solutions, Proc. Natl. Acad. Sci. USA 104, 20199 (2007).
C. Sultan, D. Stamenović, and D. E. Ingber, A computational tensegrity model predicts dynamic rheological behaviors in living cells, Ann. Biomed. Eng. 32, 520 (2004).
J. T. Hang, Y. Kang, G. K. Xu, and H. Gao, A hierarchical cellular structural model to unravel the universal power-law rheological behavior of living cells, Nat. Commun. 12, 6067 (2021).
J. T. Hang, G. K. Xu, and H. Gao, Frequency-dependent transition in power-law rheological behavior of living cells, Sci. Adv. 8, eabn6093 (2022).
M. L. Gardel, F. Nakamura, J. Hartwig, J. C. Crocker, T. P. Stossel, and D. A. Weitz, Stress-dependent elasticity of composite actin networks as a model for cell behavior, Phys. Rev. Lett. 96, 088102 (2006).
G. H. Koenderink, Z. Dogic, F. Nakamura, P. M. Bendix, F. C. MacKintosh, J. H. Hartwig, T. P. Stossel, and D. A. Weitz, An active biopolymer network controlled by molecular motors, Proc. Natl. Acad. Sci. USA 106, 15192 (2009).
N. Minc, D. Burgess, and F. Chang, Influence of cell geometry on division-plane positioning, Cell 144, 414 (2011).
J. Hu, Y. Li, Y. Hao, T. Zheng, S. K. Gupta, G. A. Parada, H. Wu, S. Lin, S. Wang, X. Zhao, R. D. Goldman, S. Cai, and M. Guo, High stretchability, strength, and toughness of living cells enabled by hyperelastic vimentin intermediate filaments, Proc. Natl. Acad. Sci. USA 116, 17175 (2019).
O. Thoumine, O. Cardoso, and J. J. Meister, Changes in the mechanical properties of fibroblasts during spreading: A micromanipulation study, Eur. Biophys. J. 28, 222 (1999).
F. Gittes, B. Mickey, J. Nettleton, and J. Howard, Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape., J. Cell Biol. 120, 923 (1993).
E. A. Evans, A new material concept for the red cell membrane, Biophys. J. 13, 926 (1973).
J. Hu, S. Jafari, Y. Han, A. J. Grodzinsky, S. Cai, and M. Guo, Size-and speed-dependent mechanical behavior in living mammalian cytoplasm, Proc. Natl. Acad. Sci. USA 114, 9529 (2017).
R. D. Kamm, A. McVittie, and M. Bathe, On the Role of continuum models in mechanobiology: Proceedings of ASME 2000 International Mechanical Engineering Congress and Exposition, Orlando, 2000.
M. L. Gardel, F. Nakamura, J. H. Hartwig, J. C. Crocker, T. P. Stossel, and D. A. Weitz, Prestressed F-actin networks cross-linked by hinged filamins replicate mechanical properties ofcells, Proc. Natl. Acad. Sci. USA 103, 1762 (2006).
K. E. Kasza, G. H. Koenderink, Y. C. Lin, C. P. Broedersz, W. Messner, F. Nakamura, T. P. Stossel, F. C. Mackintosh, and D. A. Weitz, Nonlinear elasticity of stiff biopolymers connected by flexible linkers, Phys. Rev. E 79, 041928 (2009).
D. S. Fudge, K. H. Gardner, V. T. Forsyth, C. Riekel, and J. M. Gosline, The mechanical properties of hydrated intermediate filaments: Insights from hagfish slime threads, Biophys. J. 85, 2015 (2003).
B. Fabry, G. N. Maksym, J. P. Butler, M. Glogauer, D. Navajas, N. A. Taback, E. J. Millet, and J. J. Fredberg, Time scale and other invariants of integrative mechanical behavior in living cells, Phys. Rev. E 68, 041914 (2003).
J. M. Maloney, E. Lehnhardt, A. F. Long, and K. J. Van Vliet, Mechanical fluidity of fully suspended biological cells, Biophys. J. 105, 1767 (2013).
C. P. Broedersz, and F. C. MacKintosh, Modeling semiflexible polymer networks, Rev. Mod. Phys. 86, 995 (2014).
T. Wakatsuki, M. S. Kolodney, G. I. Zahalak, and E. L. Elson, Cell mechanics studied by a reconstituted model tissue, Biophys. J. 79, 2353 (2000).
C. Verdier, Rheological properties of living materials. From cells to tissues, J. Theor. Med. 5, 67 (2003).
Y. C. Fung, Biomechanics: Mechanical Properties of Living Tissues (Springer Science & Business Media, New York, 2013).
A. J. Licup, S. Münster, A. Sharma, M. Sheinman, L. M. Jawerth, B. Fabry, D. A. Weitz, and F. C. MacKintosh, Stress controls the mechanics of collagen networks, Proc. Natl. Acad. Sci. USA 112, 9573 (2015).
S. H. Li, H. Gao, and G. K. Xu, Network dynamics of the nonlinear power-law relaxation of cell cortex, Biophys. J. 121, 4091 (2022).
N. Wang, J. P. Butler, and D. E. Ingber, Mechanotransduction across the cell surface and through the cytoskeleton, Science 260, 1124 (1993).
N. Wang, K. Naruse, D. Stamenović, J. J. Fredberg, S. M. Mijailovich, I. M. Tolić-Nørrelykke, T. Polte, R. Mannix, and D. E. Ingber, Mechanical behavior in living cells consistent with the tensegrity model, Proc. Natl. Acad. Sci. USA 98, 7765 (2001).
X. Shu, N. Li, Y. Wu, W. Li, X. Zhang, P. Li, D. Lü, S. Lü, and M. Long, Mechanotransduction of liver sinusoidal endothelial cells under varied mechanical stimuli, Acta Mech. Sin. 37, 201 (2021).
H. Wang, J. T. Hang, Z. Chang, and G. K. Xu, Static and dynamic mechanics of cell monolayers: A multi-scale structural model, Acta Mech. Sin. 38, 222006 (2022).
Acknowledgements
The work was supported by the National Natural Science Foundation of China (Grant No. 12072252), and the Fundamental Research Funds for the Central Universities.
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Dong Liang: Software, Validation, Formal analysis, Investigation, Data curation, Writing–original draft, Visualization. Jiu-Tao Hang: Conceptualization, Formal analysis, Writing–original draft, Writing–review & editing. Guang-Kui Xu: Conceptualization, Methodology, Formal analysis, Resources, Data curation, Writing–original draft, Writing–review & editing, Visualization, Project administration, Funding acquisition.
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Liang, D., Hang, JT. & Xu, GK. A structure-based cellular model reveals power-law rheology and stiffening of living cells under shear stress. Acta Mech. Sin. 39, 623129 (2023). https://doi.org/10.1007/s10409-023-23129-x
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DOI: https://doi.org/10.1007/s10409-023-23129-x