Nanoscale topography modulates corneal epithelial cell migration.

The purpose of this study was to evaluate the effect of surface topographic features that mimic the corneal epithelial basement membrane on cell migration. We used electron-beam and X-ray lithography and reactive ion etching to pattern silicon wafers with pitches (groove width plus ridge width) of nano- and microscale dimensions (pitches ranged from 400 to 4000 nm). Additionally, polyurethane patterned surfaces were created by replication molding techniques to allow for real-time imaging of migrating cells. Individual SV40-transformed human corneal epithelial cells frequently aligned with respect to the underlying surface patterns and migrated almost exclusively along grooves and ridges of all pitches. Direction of migration of individual cells on smooth surfaces was random. In cell dispersion assays, colonies of cells migrated out from initially circular zones predominantly along grooves and ridges, although there was some migration perpendicular to the ridges. On smooth surfaces, cells migrated radially, equally in all directions, maintaining circular colony shapes. We conclude that substratum features resembling the native basement membrane modulate corneal epithelial cell migration. These findings have relevance to the maintenance of corneal homeostasis and wound healing, as well as to the evolution of strategies in tissue engineering, corneal prosthesis development, and cell culture material fabrication.

[1]  P. A. Dimilla,et al.  Spreading and motility of human glioblastoma cells on sheets of silicone rubber depend on substratum compliance , 2000, Medical and Biological Engineering and Computing.

[2]  Christopher J Murphy,et al.  Cooperative modulation of neuritogenesis by PC12 cells by topography and nerve growth factor. , 2005, Biomaterials.

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

[4]  P. Prendergast,et al.  Comparative Locomotory Behavior of T Lymphocytes versus T Lymphoma Cells on Flat and Grooved Surfaces , 2003, Annals of Biomedical Engineering.

[5]  Dennis Discher,et al.  Substrate compliance versus ligand density in cell on gel responses. , 2004, Biophysical journal.

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

[7]  C. Murphy,et al.  Cell behavior on lithographically defined nanostructured substrates , 2003 .

[8]  Joyce Y. Wong,et al.  Directed Movement of Vascular Smooth Muscle Cells on Gradient-Compliant Hydrogels† , 2003 .

[9]  Amy Brock,et al.  Geometric determinants of directional cell motility revealed using microcontact printing. , 2003, Langmuir : the ACS journal of surfaces and colloids.

[10]  N. Abbott,et al.  Fabrication of polymeric substrates with well-defined nanometer-scale topography and tailored surface chemistry , 2002 .

[11]  C. Murphy,et al.  Effects of Substratum Topography on Cell Behavior , 2002 .

[12]  George M. Whitesides,et al.  Improved pattern transfer in soft lithography using composite stamps , 2002 .

[13]  C. Murphy,et al.  Electron Microscopy of the Canine Corneal Basement Membranes , 2002, Cells Tissues Organs.

[14]  J. Jansen,et al.  Modulation of epithelial tissue and cell migration by microgrooves. , 2001, Journal of biomedical materials research.

[15]  B. Dalton,et al.  Stimulation of epithelial tissue migration by certain porous topographies is independent of fluid flux. , 2001, Journal of biomedical materials research.

[16]  W. Kao,et al.  Corneal Epithelial Wound Healing , 2001, Experimental biology and medicine.

[17]  P. Moghe,et al.  Substrate microtopography can enhance cell adhesive and migratory responsiveness to matrix ligand density. , 2001, Journal of biomedical materials research.

[18]  W. Saltzman,et al.  Controlling human polymorphonuclear leukocytes motility using microfabrication technology. , 2000, Journal of biomedical materials research.

[19]  H. J. Griesser,et al.  Effect of porosity and surface hydrophilicity on migration of epithelial tissue over synthetic polymer. , 2000, Journal of biomedical materials research.

[20]  C. Murphy,et al.  Nanoscale topography of the corneal epithelial basement membrane and Descemet's membrane of the human. , 2000, Cornea.

[21]  R. Guidoin,et al.  Endothelial cell behavior on vascular prosthetic grafts: effect of polymer chemistry, surface structure, and surface treatment. , 1999, ASAIO journal.

[22]  J. Palmaz,et al.  Influence of surface topography on endothelialization of intravascular metallic material. , 1999, Journal of vascular and interventional radiology : JVIR.

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

[24]  C. Wilkinson,et al.  New depths in cell behaviour: reactions of cells to nanotopography. , 1999, Biochemical Society symposium.

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

[26]  Peter Friedl,et al.  Cell migration strategies in 3‐D extracellular matrix: Differences in morphology, cell matrix interactions, and integrin function , 1998, Microscopy research and technique.

[27]  H. J. Griesser,et al.  Surface topography can interfere with epithelial tissue migration. , 1998, Journal of biomedical materials research.

[28]  D. Brunette,et al.  Surface topography and serum concentration affect the appearance of tenascin in human gingival fibroblasts in vitro. , 1998, Experimental cell research.

[29]  P. Tresco,et al.  Relative importance of surface wettability and charged functional groups on NIH 3T3 fibroblast attachment, spreading, and cytoskeletal organization. , 1998, Journal of biomedical materials research.

[30]  V. Trinkaus-Randall,et al.  Plasma surface modification of artificial corneas for optimal epithelialization. , 1997, Journal of biomedical materials research.

[31]  T. Matsuda,et al.  Control of cell adhesion, migration, and orientation on photochemically microprocessed surfaces. , 1996, Journal of biomedical materials research.

[32]  Y. Nakayama,et al.  Surface microarchitectural design in biomedical applications: in vitro transmural endothelialization on microporous segmented polyurethane films fabricated using an excimer laser. , 1996, Journal of Biomedical Materials Research.

[33]  D. Lauffenburger,et al.  Cell Migration: A Physically Integrated Molecular Process , 1996, Cell.

[34]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[35]  H. Handa,et al.  An SV40-immortalized human corneal epithelial cell line and its characterization. , 1995, Investigative ophthalmology & visual science.

[36]  P Connolly,et al.  Cell guidance by ultrafine topography in vitro. , 1991, Journal of cell science.

[37]  R. Pilliar,et al.  Effect of the surface geometry of smooth and porous-coated titanium alloy on the orientation of fibroblasts in vitro. , 1987, Journal of biomedical materials research.

[38]  R. Buck,et al.  Cell migration in repair of mouse corneal epithelium. , 1979, Investigative ophthalmology & visual science.

[39]  Y. Sugimoto,et al.  Cell locomotion on differently charged substrates. Effects of substrate charge on locomotive speed of fibroblastic cells. , 1979, Experimental cell research.