Keratocyte mechanobiology. (November 2020)

• Record Type: Journal Article
• Authors: Petroll, W. Matthew; Varner, Victor D.; Schmidtke, David W.
• Is Part Of: Experimental eye research. Volume 200(2020)
• Publication Date: 2020-11
• Subjects: Corneal keratocytes -- Corneal stroma -- Cell mechanics -- Mechanobiology -- Extracellular matrix; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2020.108228
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: In vivo, corneal keratocytes reside within a complex 3D extracellular matrix (ECM) consisting of highly aligned collagen lamellae, growth factors, and other extracellular matrix components, and are subjected to various mechanical stimuli during developmental morphogenesis, fluctuations in intraocular pressure, and wound healing. The process by which keratocytes convert changes in mechanical stimuli (e.g. local topography, applied force, ECM stiffness) into biochemical signaling is known as mechanotransduction. Activation of the various mechanotransductive pathways can produce changes in cell migration, proliferation, and differentiation. Here we review how corneal keratocytes respond to and integrate different biochemical and biophysical factors. We first highlight how growth factors and other cytokines regulate the activity of Rho GTPases, cytoskeletal remodeling, and ultimately the mechanical phenotype of keratocytes. We then discuss how changes in the mechanical properties of the ECM have been shown to regulate keratocyte behavior in sophisticated 2D and 3D experimental models of the corneal microenvironment. Finally, we discuss how ECM topography and protein composition can modulate cell phenotypes, and review the different methods of fabricating in vitro mimics of corneal ECM topography, novel approaches for examining topographical effects in vivo, and the impact of different ECM glycoproteins and proteoglycans on keratocyte behavior. Highlights: This review highlights how ECM structure and mechanics regulate the behavior of corneal keratocytes. Changes in ECM stiffness regulate myofibroblastic transformation of keratocytes in 2D and 3D culture. Topographical cues can modulate the patterning and differentiation of cultured keratocytes. Rho GTPase-activity often coordinates the response of keratocytes to different biochemical and biomechanical cues.