The Effect of the Kind of Attachment of Primary Cilium to Cell in Its Response to the Fluid Flow: A 3D Computational Simulation

Authors

MSc/University of Tehran

Abstract

The primary cilium is an organelle which occurs singly on nearly every cell in the vertebrate body. This organelle which extends out of the cell surface like an antenna is known as cell sensor which is able to sense mechanical and chemical stimuli applied to the cell. Upon flow of fluid over the cell surface, primary cilium bends and the surrounding membrane experiences strain resulting in activation of ion channels and transfer of calcium ions. Thus, primary cilium is able to transduce mechanical stimuli to ion signals and to make the cell somehow sense the surrounding fluid flow. In this study a novel model which accommodates for both pivoting and bending of cilium in response to the fluid flow was presented. In this 3D model primary cilium is attached to the cell using a thin elastic layer which is a kind of boundary condition. The domain of the cilium is modeled with linear elastic material and finite element method was used along with fluid-structure interaction teqniques to solve the fully coupled governing equations. The maximum stress obtained at the base of the cilium is between 10 to 50 kPa depending on the stiffness of the elastic layer. Results show that application of this boundary condition causes the maximum stress and strain to move from the inner parts of the ciliary base to the lateral parts of it. That is why this model is able to better explain the sensitivity of response of the primary cilium to mechanical stimuli.

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[1] Adams M (2010) The primary cilium: An orphan organelle finds a home. Nature Education 3(9): 54.
[2] Singla V, Reiter JF (2006) The primary cilium as the cell's antenna: signaling at a sensory organelle. science 313(5787): 629-633.
[3] Marshall WF, Nonaka S (2006) Cilia: tuning in to the cell's antenna. Curr Biol 16(15): R604-R614.
[4] Fliegauf M, Benzing T, Omran H (2007) When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol 8(11): 880-893.
[5] Kovalevskij AO (1867) Entwickelungsgeschichte des Amphioxus lanceolatus, Acad. Impériale des Sciences.
[6] Mathieu PS, Bodle JC, Loboa EG (2014) 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. J Biomech 47(9): 2211-2217.
[7] Wilson PD (2004) Polycystic kidney disease. N Engl J Med 350(2): 151-164.
[8] Winyard P, Jenkins D (2011) Putative roles of cilia in polycystic kidney disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 1812(10): 1256-1262.
[9] Hoey DA, Tormey S, Ramcharan S, O'Brien FJ, Jacobs CR (2012) Primary cilia‐mediated mechanotransduction in human mesenchymal stem cells. Stem Cells 30(11): 2561-2570.
[10] Tummala P, Arnsdorf EJ, Jacobs CR (2010) The role of primary cilia in mesenchymal stem cell differentiation: a pivotal switch in guiding lineage commitment. Cell Mol Bioeng 3(3): 207-212.
[11] Bodle JC, Rubenstein CD, Phillips ME, Bernacki SH, Qi J, Banes AJ, Loboa EG (2013) Primary cilia: the chemical antenna regulating human adipose-derived stem cell osteogenesis. PLoS One 8(5): e62554.
[12] Rydholm S, Zwartz G, Kowalewski JM, Kamali-Zare P, Frisk T, Brismar H (2010) Mechanical properties of primary cilia regulate the response to fluid flow. Am J Physiol Renal Physiol 298(5): F1096-F1102.
[13] Khayyeri H, Barreto S, Lacroix D (2015) Primary cilia mechanics affects cell mechanosensation: A computational study. J Theor Biol 379: 38-46.
[14] Meriam J, Kraige L (2007) Engineering mechanics: Statics; SI Version. 6th edn. Wiley, Hoboken.
[15] Battle C, Ott CM, Burnette DT, Lippincott-Schwartz J, Schmidt CF (2015) Intracellular and extracellular forces drive primary cilia movement. Proc Natl Acad Sci U S A 112(5): 1410-1415.
[16] Abbasszadeh Rad A, Vahidi B (2016) A finite elements study on the role of primary cilia in sensing mechanical stimuli to cells by calculating their response to the fluid flow. Journal of Computational Applied Mechanics 47(1): 35-44.
[17] C. Multiphysics, 2014. Version 4.4. COMSOL, Inc., Burlington, MA, USA, pp. Fluid-Structure Interaction (fsi), Fluid Properties 1, Equation.
[18] Praetorius H, Spring KR (2001) Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 184(1): 71-79.