The Role of Thrombin and Cell Contractility in Regulating Clustering and Collective Migration of Corneal Fibroblasts in Different ECM Environments

Investigative Ophthalmology & Visual Science
Miguel Miron-MendozaW Matthew Petroll

Abstract

We previously reported that extracellular matrix composition (fibrin versus collagen) modulates the pattern of corneal fibroblast spreading and migration in 3-D culture. In this study, we investigate the role of thrombin and cell contractility in mediating these differences in cell behavior. To assess cell spreading, corneal fibroblasts were plated on top of fibrillar collagen and fibrin matrices. To assess 3-dimensional cell migration, compacted collagen matrices seeded with corneal fibroblasts were embedded inside acellular collagen or fibrin matrices. Constructs were cultured in serum-free media containing platelet-derived growth factor (PDGF), with or without thrombin, the Rho kinase inhibitor Y-27632, and/or the myosin II inhibitor blebbistatin. We used 3-dimensional and 4-dimensional imaging to assess cell mechanical behavior, connectivity and cytoskeletal organization. Thrombin stimulated increased contractility of corneal fibroblasts. Thrombin also induced Rho kinase-dependent clustering of cells plated on top of compliant collagen matrices, but not on rigid substrates. In contrast, cells on fibrin matrices coalesced into clusters even when Rho kinase was inhibited. In nested matrices, cells always migrated independentl...Continue Reading

Citations

May 18, 2017·Biomaterials Science·Gigi Chi Ting Au-YeungSubbu S Venkatraman
Apr 16, 2020·Biotechnic & Histochemistry : Official Publication of the Biological Stain Commission·Qianghua QuanChao Wang
Jun 15, 2017·Cellular and Molecular Life Sciences : CMLS·Yan ZhangMin Zhao
Jul 7, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Suitu WangTaylor H Ware
Sep 27, 2018·Journal of Functional Biomaterials·Pouriska B KivananyW Matthew Petroll
Oct 25, 2020·Scientific Reports·Noam JacobStephan R Targan
Sep 14, 2020·Experimental Eye Research·W Matthew PetrollDavid W Schmidtke

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