Quantification and significance of fluid shear stress field in biaxial cell stretching device

A widely used commercially available system for the investigation of mechanosensitivity applies a biaxial strain field to cells cultured on a compliant silicone substrate membrane stretched over a central post. As well as intended substrate strain, this device also provides a fluid flow environment for the cultured cells. In order to interpret the relevance of experiments using this device to the in vivo and clinical situation, it is essential to characterise both substrate and fluid environments. While previous work has detailed the substrate strain, the fluid shear stresses, to which bone cells are known to be sensitive, are unknown. Therefore, a fluid structure interaction computational fluid dynamics model was constructed, incorporating a finite element technique capable of capturing the contact between the post and the silicone substrate membrane, to the underside of which the pump control pressure was applied. Flow verification experiments using 10-μm-diameter fluorescent microspheres were carried out. Fluid shear stress increased approximately linearly with radius along the on-post substrate membrane, with peak values located close to the post edge. Changes in stimulation frequency and culture medium viscosity effected proportional changes in the magnitude of the fluid shear stress (peak fluid shear stresses varied in the range 0.09–3.5 Pa), with minor effects on temporal and spatial distribution. Good agreement was obtained between predicted and measured radial flow patterns. These results suggest a reinterpretation of previous data obtained using this device to include the potential for a strong role of fluid shear stress in mechanosensitivity.

[1]  E H Burger,et al.  The production of nitric oxide and prostaglandin E(2) by primary bone cells is shear stress dependent. , 2001, Journal of biomechanics.

[2]  D. Burr,et al.  Mechanotransduction in bone: osteoblasts are more responsive to fluid forces than mechanical strain. , 1997, The American journal of physiology.

[3]  Michael S Kallos,et al.  Expansion of mammalian neural stem cells in bioreactors: effect of power input and medium viscosity. , 2002, Brain research. Developmental brain research.

[4]  T A Einhorn,et al.  The cell and molecular biology of fracture healing. , 1998, Clinical orthopaedics and related research.

[5]  T J Chambers,et al.  Induction of NO and prostaglandin E2 in osteoblasts by wall-shear stress but not mechanical strain. , 1997, American journal of physiology. Endocrinology and metabolism.

[6]  D. Burr,et al.  Fluid shear-induced mechanical signaling in MC3T3-E1 osteoblasts requires cytoskeleton-integrin interactions. , 1998, American journal of physiology. Cell physiology.

[7]  Theo H Smit,et al.  Dynamic shear stress in parallel-plate flow chambers. , 2005, Journal of biomechanics.

[8]  J. Kuiper,et al.  In vitro bone growth responds to local mechanical strain in three-dimensional polymer scaffolds. , 2010, Journal of biomechanics.

[9]  Jonathan P Vande Geest,et al.  An analysis of the complete strain field within FlexercellTM membranes , 2004 .

[10]  P. Koumoutsakos,et al.  Feature point tracking and trajectory analysis for video imaging in cell biology. , 2005, Journal of structural biology.

[11]  Xiaoliu Zhang,et al.  Strain-related collagen gene expression in human osteoblast-like cells , 2005, Cell and Tissue Research.

[12]  H J Donahue,et al.  Differential effect of steady versus oscillating flow on bone cells. , 1998, Journal of biomechanics.

[13]  J. McCarthy,et al.  Uniaxial mechanical strain: an in vitro correlate to distraction osteogenesis. , 2007, The Journal of surgical research.

[14]  G N Duda,et al.  Biaxial cell stimulation: A mechanical validation. , 2009, Journal of biomechanics.

[15]  M. Ghannam,et al.  Rheological properties of carboxymethyl cellulose , 1997 .

[16]  Lin Tang,et al.  Effects of different magnitudes of mechanical strain on Osteoblasts in vitro. , 2006, Biochemical and biophysical research communications.

[17]  Jenneke Klein-Nulend,et al.  A comparison of strain and fluid shear stress in stimulating bone cell responses—a computational and experimental study , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  A. Broadus,et al.  Stretch‐Induced PTH‐Related Protein Gene Expression in Osteoblasts , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[19]  R. D. Lonsdale,et al.  AN ALGEBRAIC MULTIGRID SOLVER FOR THE NAVIER—STOKES EQUATIONS ON UNSTRUCTURED MESHES , 1993 .

[20]  A. Colombo,et al.  An analysis of the strain field in biaxial Flexcell membranes for different waveforms and frequencies , 2008, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[21]  J. Loon,et al.  Initial Stress-Kick Is Required for Fluid Shear Stress-Induced Rate Dependent Activation of Bone Cells , 2005, Annals of Biomedical Engineering.

[22]  O. Zienkiewicz The Finite Element Method In Engineering Science , 1971 .

[23]  T. Brown,et al.  Development and Experimental Validationof a Flmd/Structure-Interaction Finite Element Modelof a Vacuum-Driven Cell Culture Mechanostimulus System , 2000, Computer methods in biomechanics and biomedical engineering.