Basement membranes have many features which greatly influence cell function including specific proteins and functional groups, a reservoir of growth factors and other trophic agents, and a complex three-dimensional topography into which adherent cells extend processes and to which cells form adhesion plaques. 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 (>1um) features on cell behavior. The relevance of these """"""""large scale"""""""" studies to cell behavior in vivo is not clear since the PI's laboratories have shown the basement membrane underlying the anterior corneal epithelium to consist of a complex 3-dimensional nanoscale (>1um feature size) architecture which amplifies its surface area for cell-membrane interaction approx. 3500-4000 fold. The overall purpose of this proposal is to investigate the influence of nonoscale (<1micron) topographic features of the basement membrane underlying the anterior corneal epithelium on cell behavior. In this application, a multi-displinary approach is proposed to test 3 hypotheses using in vitro methodologies in cell biology and state of the art nanoscale fabrication techniques. Hypothesis 1: Biomimetic nonoscale topographic features of the basement membrane modulate fundamental cell behaviors. Hypothesis 2: Totally synthetic surfaces can be engineered with features (bumps v.s. pores v.s. fibers) of controlled size, distribution and surface chemistry that will modulate cell behaviors in a fashion similar to the topography of the """"""""native"""""""" basement membrane. Hypothesis 3. Nonoscale topography modulates the response of cells to other well known cytoactive compounds.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012253-03
Application #
6179037
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Fisher, Richard S
Project Start
1998-07-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$188,110
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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