Development and evaluation of microdevices for studying anisotropic biaxial cyclic stretch on cells

Mechanical effects on cells have received more and more attention in the studies of tissue engineering, cellular pathogenesis, and biomedical device design. Anisotropic biaxial cyclic stress, reminiscent of the in vivo cellular mechanical environment, may promise significant implications for biotechnology and human health. We have designed, fabricated and characterized a microdevice that imparts a variety of anisotropic biaxial cyclic strain gradients upon cells. The device is composed of an elastic membrane with microgroove patterns designed to associate cell orientation axes with biaxial strain vectors on the membrane and a Flexcell stretcher with timely controlled vacuum pressure. The stretcher generates strain profile of anisotropic biaxial microgradients on the membrane. Cell axes determined by the microgrooves are associated with the membrane strain profile to impose proper biaxial strains on cells. Using vascular smooth muscle cells as a cell model, we demonstrated that the strain anisotropy index of a cell was likely one of the determinant mechanical factors in cell structural and functional adaptations. The nuclear shape and cytoskeleton structure of smooth muscle cells were influenced by mechanical loading, but were not significantly affected by the strain anisotropy. However, cell proliferation has profound responses to strain anisotropy.

[1]  T D Brown,et al.  Techniques for mechanical stimulation of cells in vitro: a review. , 2000, Journal of biomechanics.

[2]  D. Ingber Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. , 2002, Circulation research.

[3]  E. Elson,et al.  Cellular mechanics as an indicator of cytoskeletal structure and function. , 1988, Annual review of biophysics and biophysical chemistry.

[4]  Dan L. Bader,et al.  Anisotropic, Three-Dimensional Deformation of Single Attached Cells Under Compression , 2004, Annals of Biomedical Engineering.

[5]  V. Mow,et al.  Chondrocyte deformation and local tissue strain in articular cartilage: A confocal microscopy study , 1995, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[6]  Doris A Taylor,et al.  Systolic contraction within aneurysmal rabbit myocardium following transplantation of autologous skeletal myoblasts. , 2006, The Journal of surgical research.

[7]  T. Kojima,et al.  Visualizing the Dynamics of Cerebral Aneurysms with Four-dimensional Computed Tomographic Angiography , 2005, Neurosurgery.

[8]  Masahiko Hoshijima,et al.  Anisotropic stretch-induced hypertrophy in neonatal ventricular myocytes micropatterned on deformable elastomers. , 2003, Biotechnology and bioengineering.

[9]  G. Dunn,et al.  Alignment of fibroblasts on grooved surfaces described by a simple geometric transformation. , 1986, Journal of cell science.

[10]  Albert J Banes,et al.  Ligament cells stretch-adapted on a microgrooved substrate increase intercellular communication in response to a mechanical stimulus. , 2005, Journal of biomechanics.

[11]  G Sharat Lin,et al.  Automated quantification of myocardial ischemia and wall motion defects by use of cardiac SPECT polar mapping and 4-dimensional surface rendering. , 2006, Journal of nuclear medicine technology.

[12]  J. Haga,et al.  Molecular basis of the effects of mechanical stretch on vascular smooth muscle cells. , 2007, Journal of biomechanics.

[13]  Song Li,et al.  Anisotropic mechanosensing by mesenchymal stem cells , 2006, Proceedings of the National Academy of Sciences.

[14]  D. Ingber Tensegrity II. How structural networks influence cellular information processing networks , 2003, Journal of Cell Science.

[15]  E. Foster,et al.  Validation of the wall motion score and myocardial performance indexes as novel techniques to assess cardiac function in mice after myocardial infarction. , 2007, American journal of physiology. Heart and circulatory physiology.

[16]  Peter F. Davies,et al.  Shear Stress Biology of the Endothelium , 2005, Annals of Biomedical Engineering.

[17]  M. Raff,et al.  The orientation of cell division influences cell-fate choice in the developing mammalian retina , 2003, Development.

[18]  Ivan Martin,et al.  The FASEB Journal express article 10.1096/fj.01-0656fje. Published online December 28, 2001. Cell differentiation by mechanical stress , 2022 .

[19]  A. Ooshima,et al.  Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin-angiotensin system and platelet-derived growth factor (PDGF). , 1997, Hypertension research : official journal of the Japanese Society of Hypertension.

[20]  Subra Suresh,et al.  The biomechanics toolbox: experimental approaches for living cells and biomolecules , 2003 .

[21]  Jennifer S. Park,et al.  Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells , 2004, Biotechnology and bioengineering.

[22]  Carolyn A. Lall,et al.  Beneficial and harmful effects of oscillatory mechanical strain on airway smooth muscle. , 2005, Canadian journal of physiology and pharmacology.

[23]  A. Lumsden,et al.  Roles of Hemodynamic Forces in Vascular Cell Differentiation , 2005, Annals of Biomedical Engineering.

[24]  T. Länne,et al.  Reduced pulsatile wall motion of abdominal aortic aneurysms after endovascular repair. , 1998, Journal of vascular surgery.

[25]  C Zhu,et al.  Cell mechanics: mechanical response, cell adhesion, and molecular deformation. , 2000, Annual review of biomedical engineering.

[26]  Michael Markl,et al.  Quantification of vessel wall motion and cyclic strain using cine phase contrast MRI: In vivo validation in the porcine aorta , 2004, Magnetic resonance in medicine.

[27]  E. Grood,et al.  The Strain Magnitude and Contact Guidance Determine Orientation Response of Fibroblasts to Cyclic Substrate Strains , 2000, Connective tissue research.

[28]  E. Golemis,et al.  Interdependence of cell attachment and cell cycle signaling. , 2006, Current opinion in cell biology.

[29]  Andrew D McCulloch,et al.  Micropatterned cell cultures on elastic membranes as an in vitro model of myocardium , 2006, Nature Protocols.

[30]  Dennis E. Discher,et al.  Physical plasticity of the nucleus in stem cell differentiation , 2007, Proceedings of the National Academy of Sciences.

[31]  D. Ingber Tensegrity I. Cell structure and hierarchical systems biology , 2003, Journal of Cell Science.

[32]  Farshid Guilak,et al.  The micromechanical environment of intervertebral disc cells determined by a finite deformation, anisotropic, and biphasic finite element model. , 2003, Journal of biomechanical engineering.

[33]  Douglas A. Lauffenburger,et al.  A Model for Mechanotransduction in Cardiac Muscle: Effects of Extracellular Matrix Deformation on Autocrine Signaling , 2004, Annals of Biomedical Engineering.

[34]  P. Mangeat,et al.  In vivo functional analysis of ezrin during mouse blastocyst formation. , 2001, Developmental biology.

[35]  J. Wang,et al.  Fibroblast responses to cyclic mechanical stretching depend on cell orientation to the stretching direction. , 2004, Journal of biomechanics.

[36]  P. Weinhold,et al.  Strain profiles for circular cell culture plates containing flexible surfaces employed to mechanically deform cells in vitro. , 1994, Journal of biomechanics.

[37]  J. Engel,et al.  Development and characterization of an artificial hair cell based on polyurethane elastomer and force sensitive resistors , 2005, IEEE Sensors, 2005..

[38]  Thomas J. Burkholder,et al.  Uniaxial strain system to investigate strain rate regulation in vitro , 2001 .

[39]  A. Tedgui,et al.  Cellular mechanics and gene expression in blood vessels. , 2003, Journal of biomechanics.

[40]  A. J. Reid,et al.  Endothelial cell alignment on cyclically-stretched silicone surfaces , 2004, Journal of materials science. Materials in medicine.

[41]  J. Frangos,et al.  Strain Rate Mechanotransduction in Aligned Human Vascular Smooth Muscle Cells , 2003, Annals of Biomedical Engineering.

[42]  Benjamin Geiger,et al.  Cell mechanosensitivity controls the anisotropy of focal adhesions. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[43]  C. S. Chen,et al.  Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[44]  B. Simon,et al.  Arterial mechanics in spontaneously hypertensive rats. Mechanical properties, hydraulic conductivity, and two-phase (solid/fluid) finite element models. , 1992, Circulation research.

[45]  Hiroaki Shimokawa,et al.  Statins prevent pulsatile stretch-induced proliferation of human saphenous vein smooth muscle cells via inhibition of Rho/Rho-kinase pathway. , 2005, Cardiovascular research.

[46]  P. Veltink,et al.  The mechanical properties of the rubber elastic polymer polydimethylsiloxane for sensor applications , 1997 .

[47]  Masahiro Sokabe,et al.  Dynamics of actin filaments during tension-dependent formation of actin bundles. , 2007, Biochimica et biophysica acta.

[48]  Andrew D McCulloch,et al.  Microstructured Cocultures of Cardiac Myocytes and Fibroblasts: A Two-Dimensional In Vitro Model of Cardiac Tissue , 2005, Microscopy and Microanalysis.

[49]  Manuel Théry,et al.  Cell shape and cell division. , 2006, Current opinion in cell biology.

[50]  Sumona Sarkar,et al.  Vascular tissue engineering: microtextured scaffold templates to control organization of vascular smooth muscle cells and extracellular matrix. , 2005, Acta biomaterialia.

[51]  K. Endlich,et al.  Stretch, tension and adhesion - adaptive mechanisms of the actin cytoskeleton in podocytes. , 2006, European journal of cell biology.

[52]  P. Cahill,et al.  Biomechanical regulation of hedgehog signaling in vascular smooth muscle cells in vitro and in vivo. , 2007, American journal of physiology. Cell physiology.

[53]  J. Deniset,et al.  Mechanical Stretching Stimulates Smooth Muscle Cell Growth, Nuclear Protein Import, and Nuclear Pore Expression through Mitogen-activated Protein Kinase Activation* , 2007, Journal of Biological Chemistry.

[54]  V. Hasırcı,et al.  Tissue engineering of bone on micropatterned biodegradable polyester films. , 2006, Biomaterials.

[55]  Yiider Tseng,et al.  Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration. , 2007, Biophysical journal.

[56]  Jennifer S. Park,et al.  Regulation of vascular smooth muscle cells and mesenchymal stem cells by mechanical strain. , 2006, Molecular & cellular biomechanics : MCB.