ECM stiffness modulates the proliferation but not the motility of primary corneal keratocytes in response to PDGF-BB

• Published in: Experimental eye research Vol. 220; p. 109112
• Main Authors: Iyer, Krithika S., Maruri, Daniel P., Peak, Kara E., Schmidtke, David W., Petroll, W. Matthew, Varner, Victor D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2022
• Subjects: Becaplermin - pharmacology; Biomechanics; Cell Movement; Cell Proliferation; Cells, Cultured; Corneal Keratocytes; Corneal wound healing; Freeze injury; Mechanobiology; Platelet-Derived Growth Factor; Transforming Growth Factor beta1; Corneal wound healing; Biomechanics; Platelet-derived growth factor; Freeze injury; Mechanobiology
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2022.109112

During corneal wound healing, keratocytes present within the corneal stroma become activated into a repair phenotype upon the release of growth factors, such as transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor-BB (PDGF-BB). The process of injury and repair can lead to changes in the mechanical properties of the tissue, and previous work has shown that the TGF-β1-mediated myofibroblast differentiation of corneal keratocytes depends on substratum stiffness. It is still unclear, however, if changes in stiffness can modulate keratocyte behavior in response to other growth factors, such as PDGF-BB. Here, we used a polyacrylamide (PA) gel system to determine whether changes in stiffness influence the proliferation and motility of primary corneal keratocytes treated with PDGF-BB. In the presence of PDGF-BB, cells on stiffer substrata exhibited a more elongated morphology and had higher rates of proliferation than cells in a more compliant microenvironment. Using a freeze-injury to assay cell motility, however, we did not observe any stiffness-dependent differences in the migration of keratocytes treated with PDGF-BB. Taken together, these data highlight the importance of biophysical cues during corneal wound healing and suggest that keratocytes respond differently to changes in ECM stiffness in the presence of different growth factors.
•Changes in substratum stiffness modulate keratocyte spreading and elongation in response to PDGF-BB.•A stiffer microenvironment promotes an increase in PDGF-BB-mediated keratocyte proliferation.•Substratum stiffness does not affect the motility of PDGF-BB-treated keratocytes in a freeze injury assay of cell migration.