Corneal epithelial cells rest upon a basement membrane, which represents a unique specialization of the extracellular matrix. Basement membranes have many features that greatly influence cell function including a complex three-dimensional topography. The three-dimensional topography of the underlying substrate independent of specific receptor-ligand interactions, has been recently shown to influence fundamental cell behaviors. The majority of studies conducted to date have evaluated the effect of large scale (> 1 um) features on cell behavior. The relevance of these """"""""large-scale"""""""" studies to cell behavior in vivo is not clear since our laboratories have shown the basement membrane underlying the anterior corneal epithelium to consist of a complex 3-dimensional nanoscale (< 1 micron feature size) architecture which amplifies its surface area for cell-membrane interaction. Additionally, we have shown that corneal epithelial cells respond differently to these large-scale features than to much finer nanoscale features that are more representative of the topographic features encountered in vivo. The overall purpose of this proposal is to investigate the ability of nanoscale (< 1 micron) topographic features to modulate fundamental cell behaviors. In this application, a multi-disciplinary approach is proposed to test 3 hypotheses using in vitro methodologies in cell biology and state-of-the-art nanoscale fabrication techniques. Hypothesis 1: Totally synthetic surfaces can be engineered through controlled fabrication with biologically relevant feature types (bumps vs. pores vs. fibers), dimensions and distributions that will modulate corneal epithelial cell behaviors. Hypothesis 2: Biomimetic nanoscale topographic features of the basement membrane modulate fundamental corneal cell behaviors. Hypothesis 3: Cytoactive compounds interact with Nanoscale topography to modulate corneal epithelial cell behavior.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY012253-05
Application #
6544369
Study Section
Special Emphasis Panel (ZRG1-MDCN-1 (03))
Program Officer
Fisher, Richard S
Project Start
1998-07-01
Project End
2006-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
5
Fiscal Year
2002
Total Cost
$327,375
Indirect Cost
Name
University of Wisconsin Madison
Department
Surgery
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Gao, Jing; Raghunathan, Vijay Krishna; Reid, Brian et al. (2015) Biomimetic stochastic topography and electric fields synergistically enhance directional migration of corneal epithelial cells in a MMP-3-dependent manner. Acta Biomater 12:102-112
Thomasy, Sara M; Raghunathan, Vijay Krishna; Winkler, Moritz et al. (2014) Elastic modulus and collagen organization of the rabbit cornea: epithelium to endothelium. Acta Biomater 10:785-91
Raghunathan, Vijay Krishna; McKee, Clayton T; Tocce, Elizabeth J et al. (2013) Nuclear and cellular alignment of primary corneal epithelial cells on topography. J Biomed Mater Res A 101:1069-79
Dreier, Britta; Raghunathan, Vijaya Krishna; Russell, Paul et al. (2012) Focal adhesion kinase knockdown modulates the response of human corneal epithelial cells to topographic cues. Acta Biomater 8:4285-94
Myrna, Kathern E; Mendonsa, Rima; Russell, Paul et al. (2012) Substratum topography modulates corneal fibroblast to myofibroblast transformation. Invest Ophthalmol Vis Sci 53:811-6
Pot, Simon A; Liliensiek, Sara J; Myrna, Kathern E et al. (2010) Nanoscale topography-induced modulation of fundamental cell behaviors of rabbit corneal keratocytes, fibroblasts, and myofibroblasts. Invest Ophthalmol Vis Sci 51:1373-81
Soofi, Shauheen S; Last, Julie A; Liliensiek, Sara J et al. (2009) The elastic modulus of Matrigel as determined by atomic force microscopy. J Struct Biol 167:216-9
Last, Julie A; Liliensiek, Sara J; Nealey, Paul F et al. (2009) Determining the mechanical properties of human corneal basement membranes with atomic force microscopy. J Struct Biol 167:19-24
Ghoghawala, S Y; Mannis, M J; Murphy, C J et al. (2007) Economical LED based, real-time, in vivo imaging of murine corneal wound healing. Exp Eye Res 84:1031-8
Karuri, Nancy W; Porri, Teresa J; Albrecht, Ralph M et al. (2006) Nano- and microscale holes modulate cell-substrate adhesion, cytoskeletal organization, and -beta1 integrin localization in SV40 human corneal epithelial cells. IEEE Trans Nanobioscience 5:273-80

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