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Article

Coupling of Fibrin Reorganization and Fibronectin Patterning by Corneal Fibroblasts in Response to PDGF BB and TGFβ1

Department of Ophthalmology, UT Southwestern Medical Center, Dallas, TX 75390, USA
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Author to whom correspondence should be addressed.
Bioengineering 2020, 7(3), 89; https://doi.org/10.3390/bioengineering7030089
Received: 26 May 2020 / Revised: 2 August 2020 / Accepted: 5 August 2020 / Published: 7 August 2020
(This article belongs to the Special Issue Extracellular Matrix in Wound Healing)
We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell-induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGFβ1 stimulated global fibrin matrix contraction (p < 0.005); however, the cell and matrix patterning were different. We found that, during PDGF BB-induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (p < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (p < 0.001). Taken together, our results show that cell-induced extracellular matrix (ECM) reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery. View Full-Text
Keywords: fibronectin; corneal fibroblasts; fibrin; 3-D matrices; collective cell migration fibronectin; corneal fibroblasts; fibrin; 3-D matrices; collective cell migration
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MDPI and ACS Style

Miron-Mendoza, M.; Vazquez, D.; García-Rámila, N.; Ikebe, H.R.; Petroll, W.M. Coupling of Fibrin Reorganization and Fibronectin Patterning by Corneal Fibroblasts in Response to PDGF BB and TGFβ1. Bioengineering 2020, 7, 89. https://doi.org/10.3390/bioengineering7030089

AMA Style

Miron-Mendoza M, Vazquez D, García-Rámila N, Ikebe HR, Petroll WM. Coupling of Fibrin Reorganization and Fibronectin Patterning by Corneal Fibroblasts in Response to PDGF BB and TGFβ1. Bioengineering. 2020; 7(3):89. https://doi.org/10.3390/bioengineering7030089

Chicago/Turabian Style

Miron-Mendoza, Miguel, Dalia Vazquez, Nerea García-Rámila, Hikaru R. Ikebe, and W. M. Petroll 2020. "Coupling of Fibrin Reorganization and Fibronectin Patterning by Corneal Fibroblasts in Response to PDGF BB and TGFβ1" Bioengineering 7, no. 3: 89. https://doi.org/10.3390/bioengineering7030089

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