Working Paper Article Version 2 This version is not peer-reviewed

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

Version 1 : Received: 4 July 2020 / Approved: 5 July 2020 / Online: 5 July 2020 (14:45:36 CEST)
Version 2 : Received: 5 August 2020 / Approved: 6 August 2020 / Online: 6 August 2020 (00:20:04 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Bioengineering 2020, 7, 89
DOI: 10.3390/bioengineering7030089

Abstract

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 TGF stimulated global fibrin matrix contraction (P < 0.005), however 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 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.

Subject Areas

fibronectin; corneal fibroblasts; fibrin; 3-D matrices; collective cell migration

Comments (1)

Comment 1
Received: 6 August 2020
Commenter: W. Matthew Petroll
Commenter's Conflict of Interests: Author
Comment: Order of authors corrected. Added supplemental Figure 1. Changes to text of conlcusions. Changes to Figure 1 legend.
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