Journal of Computational Applied Mechanics

A finite elements study on the role of primary cilia in sensing mechanical stimuli to cells by calculating their response to the fluid flow

Document Type : Research Paper

Authors

1 Division of Biomedical Engineering, Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran

2 Faculty of New Sciences and Technologies, University of Tehran

Abstract

The primary cilium which is an organelle in nearly every cell in the vertebrate body extends out of the cell surface like an antenna and is known as cell sensor of mechanical and chemical stimuli. In previous numerical simulations, researchers modeled this organelle as a cantilevered beam attached to the cell surface. In the present study, however, we present a novel model that accommodates for both pivoting and bending of primary cilium in response to the fluid flow. In this model, primary cilium is attached to the cell using a thin elastic layer. This layer, which comprises the bottom boundary of the cilium, provides the possibility of pivoting of the cilium around its base so that we are able to analyze the other part of ciliary response to the fluid flow. In this study, we have used finite element method and fluid-structure interaction techniques to simulate the problem. Domains of solid cilium and the surrounding fluid were meshed using triangular elements. The governing equations in this problem were fully coupled and were solved by the direct method. Graphs of maximum stress in the cilium base versus elastic constant of the thin layer depict two different trends. By scrutinizing colored plots of stress distribution in the cilium base it is construed that these trends represent two different mechanisms in ciliary deformation due to the flow of the fluid. In case of low elasticity constants, for which attachment of the cilium to the cell is soft, pivoting mechanism is essential, while in case of harder attachments, bending mechanism dominates.

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Main Subjects

[1]           V. Singla, J. F. Reiter, The primary cilium as the cell's antenna: signaling at a sensory organelle, science, Vol. 313, No. 5787, pp. 629-633, 2006.
[2]           P. Winyard, D. Jenkins, Putative roles of cilia in polycystic kidney disease, Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, Vol. 1812, No. 10, pp. 1256-1262, 2011.
[3]           D. A. Hoey, S. Tormey, S. Ramcharan, F. J. O'Brien, C. R. Jacobs, Primary Cilia‐Mediated Mechanotransduction in Human Mesenchymal Stem Cells, Stem cells, Vol. 30, No. 11, pp. 2561-2570, 2012.
[4]           P. Tummala, E. J. Arnsdorf, C. R. Jacobs, The role of primary cilia in mesenchymal stem cell differentiation: a pivotal switch in guiding lineage commitment, Cellular and molecular bioengineering, Vol. 3, No. 3, pp. 207-212, 2010.
[5]           J. C. Bodle, C. D. Rubenstein, M. E. Phillips, S. H. Bernacki, J. Qi, A. J. Banes, E. G. Loboa, Primary cilia: the chemical antenna regulating human adipose-derived stem cell osteogenesis, 2013.
[6]           A. D. Hanson, S. W. Marvel, S. H. Bernacki, A. J. Banes, J. van Aalst, E. G. Loboa, Osteogenic effects of rest inserted and continuous cyclic tensile strain on hASC lines with disparate osteodifferentiation capabilities, Annals of biomedical engineering, Vol. 37, No. 5, pp. 955-965, 2009.
[7]           M. E. Wall, A. Rachlin, C. A. Otey, E. G. Loboa, Human adipose-derived adult stem cells upregulate palladin during osteogenesis and in response to cyclic tensile strain, American Journal of Physiology-Cell Physiology, Vol. 293, No. 5, pp. C1532-C1538, 2007.
[8]           S. Diederichs, S. Böhm, A. Peterbauer, C. Kasper, T. Scheper, M. Van Griensven, Application of different strain regimes in two‐dimensional and three‐dimensional adipose tissue–derived stem cell cultures induces osteogenesis: Implications for bone tissue engineering, Journal of Biomedical Materials Research Part A, Vol. 94, No. 3, pp. 927-936, 2010.
[9]           S. Rydholm, G. Zwartz, J. M. Kowalewski, P. Kamali-Zare, T. Frisk, H. Brismar, Mechanical properties of primary cilia regulate the response to fluid flow, American Journal of Physiology-Renal Physiology, Vol. 298, No. 5, pp. F1096-F1102, 2010.
[10]         M. Fliegauf, T. Benzing, H. Omran, When cilia go bad: cilia defects and ciliopathies, Nature reviews Molecular cell biology, Vol. 8, No. 11, pp. 880-893, 2007.
[11]         A. D. Güler, H. Lee, T. Iida, I. Shimizu, M. Tominaga, M. Caterina, Heat-evoked activation of the ion channel, TRPV4, The Journal of neuroscience, Vol. 22, No. 15, pp. 6408-6414, 2002.
[12]         M. Köttgen, B. Buchholz, M. A. Garcia-Gonzalez, F. Kotsis, X. Fu, M. Doerken, C. Boehlke, D. Steffl, R. Tauber, T. Wegierski, TRPP2 and TRPV4 form a polymodal sensory channel complex, The Journal of cell biology, Vol. 182, No. 3, pp. 437-447, 2008.
[13]         H. Praetorius, K. R. Spring, Bending the MDCK cell primary cilium increases intracellular calcium, The Journal of membrane biology, Vol. 184, No. 1, pp. 71-79, 2001.
[14]         B. K. Yoder, X. Hou, L. M. Guay-Woodford, The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia, Journal of the American Society of Nephrology, Vol. 13, No. 10, pp. 2508-2516, 2002.
[15]         S. M. Nauli, F. J. Alenghat, Y. Luo, E. Williams, P. Vassilev, X. Li, A. E. Elia, W. Lu, E. M. Brown, S. J. Quinn, Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells, Nature genetics, Vol. 33, No. 2, pp. 129-137, 2003.
[16]         P. S. Mathieu, J. C. Bodle, E. G. Loboa, Primary cilium mechanotransduction of tensile strain in 3D culture: Finite element analyses of strain amplification caused by tensile strain applied to a primary cilium embedded in a collagen matrix, Journal of biomechanics, Vol. 47, No. 9, pp. 2211-2217, 2014.
[17]         C. Battle, C. M. Ott, D. T. Burnette, J. Lippincott-Schwartz, C. F. Schmidt, Intracellular and extracellular forces drive primary cilia movement, Proceedings of the National Academy of Sciences, Vol. 112, No. 5, pp. 1410-1415, 2015.
[18]         H. Khayyeri, S. Barreto, D. Lacroix, Primary cilia mechanics affects cell mechanosensation: A computational study, Journal of theoretical biology, Vol. 379, pp. 38-46, 2015.
[19]         C. Multiphysics, 2014. Version 4.4. COMSOL, Inc., Burlington, MA, USA, pp. Fluid-Structure Interaction (fsi), Fluid Properties 1, Equation.
[20]         C. Multiphysics, 2014. Version 4.4. COMSOL, Inc., Burlington, MA, USA, pp. Fluid-Structure Interaction (fsi), Fluid-Solid Interface Boundary 1, Equation.
[21]         C. Multiphysics, 2014. Version 4.4. COMSOL, Inc., Burlington, MA, USA, pp. Fluid-Structure Interaction (fsi), Linear Elastic Material 1, Equation.
[22]         C. Multiphysics, 2014. Version 4.4. COMSOL, Inc., Burlington, MA, USA, pp. Fluid-Structure Interaction (fsi), Fixed Constraint 1, Equation.
[23]         C. Multiphysics, 2014. Version 4.4. COMSOL, Inc., Burlington, MA, USA, pp. Fluid-Structure Interaction (fsi), Spring Foundation 1, Equation.
[24]        Y. Enuka, I. Hanukoglu, O. Edelheit, H. Vaknine, A. Hanukoglu, Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways, Histochemistry and cell biology, Vol. 137, No. 3, pp. 339-353, 2012.
Journal of Computational Applied Mechanics
Volume 47, Issue 1
June 2016
Pages 35-44
  • Receive Date: 07 February 2016
  • Revise Date: 06 April 2016
  • Accept Date: 30 April 2016