# Regulation of Corneal Keratocyte Differentiation through the Integration of Biochemical, Biomechanical and Topographic Cues

> **NIH NIH R01** · UNIVERSITY OF TEXAS DALLAS · 2020 · $368,349

## Abstract

Project Summary
Corneal keratocytes reside between the collagen lamellae in the cornea stroma, and are responsible
for secreting ECM components required to maintain normal corneal structure and transparency.
Through their interactions with the extracellular matrix (ECM), stromal keratocytes play a central role in
fundamental biological processes such as developmental morphogenesis and wound healing. Such
interactions also are also important in the field of tissue engineering, where it is necessary to either
modulate cell and ECM patterning to produce specific matrix architectures. While much is known
regarding the effects of growth factors on keratocyte differentiation on rigid 2-D rigid substrates, corneal
keratocytes reside in a complex ECM environment in vivo, which includes a combination of mechanical,
topographical and biochemical cues. ECM stiffness, topography and protein composition have all
been shown to modulate keratocyte differentiation, contractility and patterning. However, there
are still significant gaps in our knowledge of how multiple stimuli are integrated to produce
specific cell phenotypes. The overall goal of this proposal is to develop and test novel 2D and 3D
experimental platforms that will allow us to systematically incorporate combinations of both soluble and
non-soluble cues.
In Specific Aim 1 we will determine how substrate elasticity modulates the keratocyte response to
soluble biochemical cues by fabricating tunable polyacrylamide substrates over a range of mechanical
stiffness values and using traction force microscopy, quantitative immunofluorescence imaging and
biochemical assays to evaluate changes in keratocyte differentiation. In Aim 2 we will determine how
substrate topography and composition modulates the keratocyte response to biochemical and
biomechanical cues using substrates with aligned fibrillar collagen combined with other key ECM
proteins. In Aim 3 we will determine how substrate dimensionality (2-D versus 3-D) modulates the
keratocyte response to biochemical, biomechanical and topographic cues by fabricating novel 3D
sandwich constructs that present these cues to both the ventral and dorsal surfaces of cells.
These new experimental platforms can be used to identify, isolate, and investigate the role of key
biophysical signaling pathways on the differentiation of keratocytes (e.g. quiescent, migratory,
regenerative and fibrotic phenotypes). Knowledge obtained could aid in the development of targeted
anti-fibrosis therapies, as well as guide tissue engineering approaches to developing stromal tissue
replacements. Importantly, the experimental models developed could have broad application in
other fields where biophysical cues and mechanotransduction are known to have a profound
impact on cell patterning and behavior, such as developmental and cancer biology.

## Key facts

- **NIH application ID:** 9933928
- **Project number:** 5R01EY030190-02
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** DAVID W SCHMIDTKE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,349
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933928

## Citation

> US National Institutes of Health, RePORTER application 9933928, Regulation of Corneal Keratocyte Differentiation through the Integration of Biochemical, Biomechanical and Topographic Cues (5R01EY030190-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9933928. Licensed CC0.

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