Nanopattern-induced changes in morphology and motility of smooth muscle cells.

Cells are known to be surrounded by nanoscale topography in their natural extracellular environment. The cell behavior, including morphology, proliferation, and motility of bovine pulmonary artery smooth muscle cells (SMC) were studied on poly(methyl methacrylate) (PMMA) and poly(dimethylsiloxane) (PDMS) surfaces comprising nanopatterned gratings with 350 nm linewidth, 700 nm pitch, and 350 nm depth. More than 90% of the cells aligned to the gratings, and were significantly elongated compared to the SMC cultured on non-patterned surfaces. The nuclei were also elongated and aligned. Proliferation of the cells was significantly reduced on the nanopatterned surfaces. The polarization of microtubule organizing centers (MTOC), which are associated with cell migration, of SMC cultured on nanopatterned surfaces showed a preference towards the axis of cell alignment in an in vitro wound healing assay. In contrast, the MTOC of SMC on non-patterned surfaces preferentially polarized towards the wound edge. It is proposed that this nanoimprinting technology will provide a valuable platform for studies in cell-substrate interactions and for development of medical devices with nanoscale features.

[1]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[2]  Matthew J Dalby,et al.  Increasing fibroblast response to materials using nanotopography: morphological and genetic measurements of cell response to 13-nm-high polymer demixed islands. , 2002, Experimental cell research.

[3]  D J Mooney,et al.  Control of microtubule assembly by extracellular matrix and externally applied strain. , 2001, American journal of physiology. Cell physiology.

[4]  Thomas J Webster,et al.  Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic acid) with nano-structured surface features. , 2004, Biomaterials.

[5]  A. Yee,et al.  Reversal imprinting by transferring polymer from mold to substrate , 2002 .

[6]  Mathis O. Riehle,et al.  The use of materials patterned on a nano- and micro-metric scale in cellular engineering , 2002 .

[7]  Robert M Nerem,et al.  Tissue engineering: confronting the transplantation crisis. , 2003, Advances in experimental medicine and biology.

[8]  A Curtis,et al.  Nantotechniques and approaches in biotechnology. , 2001, Trends in biotechnology.

[9]  Wisniewski,et al.  Methods for reducing biosensor membrane biofouling. , 2000, Colloids and surfaces. B, Biointerfaces.

[10]  A. Hall,et al.  Integrin-Mediated Activation of Cdc42 Controls Cell Polarity in Migrating Astrocytes through PKCζ , 2001, Cell.

[11]  A. Yee,et al.  Nanoimprinting over topography and multilayer three-dimensional printing , 2002 .

[12]  A Curtis,et al.  Synergistic and hierarchical adhesive and topographic guidance of BHK cells. , 1996, Experimental cell research.

[13]  W. Godwin.  Article in Press , 2000 .

[14]  M C Davies,et al.  Spatially controlled cell engineering on biodegradable polymer surfaces , 1998, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[15]  K. Mostov.  Faculty Opinions recommendation of Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. , 2001 .

[16]  A Curtis,et al.  Activation of macrophage‐like cells by multiple grooved substrata. Topographical control of cell behaviour. , 1995, Cell biology international.

[17]  Matthew J Dalby,et al.  Nucleus alignment and cell signaling in fibroblasts: response to a micro-grooved topography. , 2003, Experimental cell research.

[18]  A Compston,et al.  Guidance of oligodendrocytes and their progenitors by substratum topography. , 1995, Journal of cell science.

[19]  Nikolaj Gadegaard,et al.  Investigating filopodia sensing using arrays of defined nano-pits down to 35 nm diameter in size. , 2004, The international journal of biochemistry & cell biology.

[20]  B D Boyan,et al.  Role of material surfaces in regulating bone and cartilage cell response. , 1996, Biomaterials.

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

[22]  Dorian Liepmann,et al.  Regulation of vascular smooth muscle cells by micropatterning. , 2003, Biochemical and biophysical research communications.

[23]  Thomas J Webster,et al.  Polymers with nano-dimensional surface features enhance bladder smooth muscle cell adhesion. , 2003, Journal of biomedical materials research. Part A.

[24]  A Curtis,et al.  Guidance and activation of murine macrophages by nanometric scale topography. , 1996, Experimental cell research.

[25]  H. Sheardown,et al.  Interactions of corneal epithelial cells and surfaces modified with cell adhesion peptide combinations , 2002, Journal of biomaterials science. Polymer edition.

[26]  L. Machesky,et al.  Microtubule involvement in NIH 3T3 Golgi and MTOC polarity establishment , 2003, Journal of Cell Science.

[27]  Eva L Feldman,et al.  Substrate patterning: an emerging technology for the study of neuronal behavior , 2003, Experimental Neurology.

[28]  C. Wilkinson,et al.  Reactions of cells to topography. , 1998, Journal of biomaterials science. Polymer edition.

[29]  Kevin E. Healy,et al.  Engineering gene expression and protein synthesis by modulation of nuclear shape , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[30]  S. Boxer,et al.  Cell adhesion to protein-micropatterned-supported lipid bilayer membranes. , 2001, Journal of biomedical materials research.

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

[32]  C. Wilkinson,et al.  Nanotechniques and approaches in biotechnology , 2001 .

[33]  A S G Curtis,et al.  Polymer-demixed nanotopography: control of fibroblast spreading and proliferation. , 2002, Tissue engineering.

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

[35]  Erkki Ruoslahti,et al.  Cell spreading controls endoplasmic and nuclear calcium: A physical gene regulation pathway from the cell surface to the nucleus , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  D. L. Taylor,et al.  Topographical and Physicochemical Modification of Material Surface to Enable Patterning of Living Cells , 2001, Critical reviews in biotechnology.

[37]  C. Wilkinson,et al.  Role of the cytoskeleton in the reaction of fibroblasts to multiple grooved substrata. , 1995, Cell motility and the cytoskeleton.

[38]  P. Clark,et al.  Alignment of myoblasts on ultrafine gratings inhibits fusion in vitro. , 2002, The international journal of biochemistry & cell biology.

[39]  G. Owens,et al.  Molecular regulation of vascular smooth muscle cell differentiation in development and disease. , 2004, Physiological reviews.

[40]  P Connolly,et al.  Novel Methods for the Guidance and Monitoring of Single Cells and Simple Networks in Culture , 1987, Journal of Cell Science.

[41]  P. F. Nealey,et al.  Nanoscale topography of the basement membrane underlying the corneal epithelium of the rhesus macaque , 1999, Cell and Tissue Research.

[42]  C. Wilkinson.  Nanostructures in biology , 1995 .

[43]  G. D. Das,et al.  Contact guidance and migratory cells in the developing cerebellum. , 1974, Brain research.

[44]  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.

[45]  S. Mallapragada,et al.  Oriented astroglial cell growth on micropatterned polystyrene substrates. , 2004, Biomaterials.

[46]  A. Curtis,et al.  CONTROL OF CELL BEHAVIOR: TOPOLOGICAL FACTORS. , 1964, Journal of the National Cancer Institute.

[47]  J. Miner,et al.  Cell Elongation Induces Laminin α2 Chain Expression in Mouse Embryonic Mesenchymal Cells , 1999, The Journal of cell biology.

[48]  T. Desai,et al.  Inhibition of fibroblast proliferation in cardiac myocyte cultures by surface microtopography. , 2003, American journal of physiology. Cell physiology.