The control of cell adhesion and viability by zinc oxide nanorods.

The ability to control the behavior of cells that interact with implanted biomaterials is desirable for the success of implanted devices such as biosensors or drug delivery devices. There is a need to develop materials that can limit the adhesion and viability of cells on implanted biomaterials. In this study, we investigated the use of zinc oxide (ZnO) nanorods for modulating the adhesion and viability of NIH 3T3 fibroblasts, umbilical vein endothelial cells, and capillary endothelial cells. Cells adhered far less to ZnO nanorods than the corresponding ZnO flat substrate. The few cells that adhered to ZnO nanorods were rounded and not viable compared to the flat ZnO substrate. Cells were unable to assemble focal adhesions and stress fibers on nanorods. Scanning electron microscopy indicated that cells were not able to assemble lamellipodia on nanorods. Time-lapse imaging revealed that cells that initially adhered to nanorods were not able to spread. This suggests that it is the lack of initial spreading, rather than long-term exposure to ZnO that causes cell death. We conclude that ZnO nanorods are potentially useful as an adhesion-resistant biomaterial capable of reducing viability in anchorage-dependent cells.

[1]  Donald E Ingber,et al.  Mechanical forces alter zyxin unbinding kinetics within focal adhesions of living cells , 2006, Journal of cellular physiology.

[2]  Nikolaj Gadegaard,et al.  The response of fibroblasts to hexagonal nanotopography fabricated by electron beam lithography. , 2008, Journal of biomedical materials research. Part A.

[3]  Low Temperature (< 100{degree sign}C) Patterned Growth of ZnO Nanorod Arrays on Si , 2007 .

[4]  Shuichi Takayama,et al.  Fabrication of reconfigurable protein matrices by cracking , 2005, Nature materials.

[5]  Magnus Willander,et al.  ZnO nanorods as an intracellular sensor for pH measurements , 2007 .

[6]  Peidong Yang,et al.  Low-temperature wafer-scale production of ZnO nanowire arrays. , 2003, Angewandte Chemie.

[7]  C. Murphy,et al.  Epithelial contact guidance on well-defined micro- and nanostructured substrates , 2003, Journal of Cell Science.

[8]  Peidong Yang,et al.  Interfacing silicon nanowires with mammalian cells. , 2007, Journal of the American Chemical Society.

[9]  Benjamin Geiger,et al.  Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize. , 2006, Current opinion in cell biology.

[10]  Joachim P Spatz,et al.  Activation of integrin function by nanopatterned adhesive interfaces. , 2004, Chemphyschem : a European journal of chemical physics and physical chemistry.

[11]  Wei He,et al.  Grafting of gelatin on electrospun poly(caprolactone) nanofibers to improve endothelial cell spreading and proliferation and to control cell Orientation. , 2005, Tissue engineering.

[12]  Donald E Ingber,et al.  Directional control of cell motility through focal adhesion positioning and spatial control of Rac activation , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[13]  John C. Rutledge,et al.  Induction of Inflammation in Vascular Endothelial Cells by Metal Oxide Nanoparticles: Effect of Particle Composition , 2006, Environmental health perspectives.

[14]  Stephen J Pearton,et al.  Penetrating living cells using semiconductor nanowires. , 2007, Trends in biotechnology.

[15]  F. Ren,et al.  Low temperature (<100 °C) patterned growth of ZnO nanorod arrays on Si , 2007 .

[16]  Benjamin M. Wu,et al.  Cell interaction with three-dimensional sharp-tip nanotopography. , 2007, Biomaterials.

[17]  C J Murphy,et al.  Effects of synthetic micro- and nano-structured surfaces on cell behavior. , 1999, Biomaterials.

[18]  A S G Curtis,et al.  Morphological and microarray analysis of human fibroblasts cultured on nanocolumns produced by colloidal lithography. , 2005, European cells & materials.

[19]  C J Murphy,et al.  Nanoscale topography modulates corneal epithelial cell migration. , 2003, Journal of biomedical materials research. Part A.

[20]  F. Re,et al.  Inhibition of anchorage-dependent cell spreading triggers apoptosis in cultured human endothelial cells , 1994, The Journal of cell biology.

[21]  David P. Norton,et al.  pH measurements with single ZnO nanorods integrated with a microchannel , 2005 .

[22]  Kam W Leong,et al.  Nanopattern-induced changes in morphology and motility of smooth muscle cells. , 2005, Biomaterials.

[23]  C J Murphy,et al.  The scale of substratum topographic features modulates proliferation of corneal epithelial cells and corneal fibroblasts. , 2006, Journal of biomedical materials research. Part A.

[24]  Hoi Sing Kwok,et al.  OPTICAL PROPERTIES OF EPITAXIALLY GROWN ZINC OXIDE FILMS ON SAPPHIRE BY PULSED LASER DEPOSITION , 1999 .

[25]  C. S. Chen,et al.  Geometric control of cell life and death. , 1997, Science.

[26]  Benjamin Geiger,et al.  Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. , 2007, Biophysical journal.

[27]  F. Bäckhed,et al.  Nanoscale features influence epithelial cell morphology and cytokine production. , 2003, Biomaterials.

[28]  Ning Wang,et al.  Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[29]  A. Kornowski,et al.  Self‐Assembly of ZnO: From Nanodots to Nanorods. , 2002 .

[30]  C. Nicolini,et al.  Carbon nanotube biocompatibility with cardiac muscle cells , 2006 .

[31]  Thomas J Webster,et al.  The role of nanometer and sub-micron surface features on vascular and bone cell adhesion on titanium. , 2008, Biomaterials.

[32]  Carlos E Semino,et al.  The effect of functionalized self-assembling peptide scaffolds on human aortic endothelial cell function. , 2005, Biomaterials.

[33]  Joshua E. Goldberger,et al.  Low‐Temperature Wafer‐Scale Production of ZnO Nanowire Arrays. , 2003 .

[34]  Nitin Kumar,et al.  Nanoscale ZnO‐Enhanced Fluorescence Detection of Protein Interactions , 2006 .

[35]  Christopher J Murphy,et al.  Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells , 2004, Journal of Cell Science.

[36]  E. A. Cavalcanti-Adam,et al.  Cellular Chemomechanics at Interfaces: Sensing, Integration and Response{ , 2006 .

[37]  Lifeng Chi,et al.  Osteoblast alignment, elongation and migration on grooved polystyrene surfaces patterned by Langmuir-Blodgett lithography. , 2005, Biomaterials.

[38]  Christopher J Murphy,et al.  The effect of environmental factors on the response of human corneal epithelial cells to nanoscale substrate topography. , 2006, Biomaterials.

[39]  M. Willander,et al.  ZnO nanorods as an intracellular sensor for pH measurements. , 2009, Methods in molecular biology.

[40]  M. Michikawa,et al.  Apolipoprotein E4 induces neuronal cell death under conditions of suppressed de novo cholesterol synthesis , 1998, Journal of neuroscience research.

[41]  Benjamin Geiger,et al.  Molecular engineering of cellular environments: cell adhesion to nano-digital surfaces. , 2007, Methods in cell biology.

[42]  Nitin Kumar,et al.  Highly sensitive biomolecular fluorescence detection using nanoscale ZnO platforms. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[43]  Newell R Washburn,et al.  High-throughput investigation of osteoblast response to polymer crystallinity: influence of nanometer-scale roughness on proliferation. , 2004, Biomaterials.

[44]  Joachim P Spatz,et al.  Mimicking cellular environments by nanostructured soft interfaces. , 2007, Nano letters.

[45]  A S G Curtis,et al.  In vitro reaction of endothelial cells to polymer demixed nanotopography. , 2002, Biomaterials.