Mechanobiology of elastic tissues

Coordinator: R. Debret

Participants: G. Aimond, A. Berthier, B. Fromy, M. Lo, K. Liu, J. Sohier, C. Ya

Biological soft tissues, such as skin, cardiovascular system, lungs and ligaments, all require to be deformable. This characteristic is governed by physical laws of viscoelasticity brought by the natural biopolymers composing the extracellular matrix. Indeed, the collagen fibrillar networks ensure the maintenance and the resistance of the tissues, the glycosaminoglycans control the viscosity of the medium, and the elastic fibers ensure the reversible deformability of the soft tissues. Unfortunately, the latter degrade progressively with time because the cellular programs allowing their synthesis (elastogenesis) are deactivated after growth.

Based on the analysis of pathological biological material (cutis laxa, Williams-Beuren syndrome, …), this project aims at:

  • understanding the mechanisms of elastogenesis regulation;
  • decrypting the impact of elasticity loss upon gene reprogramming in resident cells.

In parallel, we are developing solutions to reinduce elastogenesis or to mimic elastic tissues:

  • by a pharmacological approach targeting the cellular pathways leading to elastogenesis;
  • by using a synthetic elastic protein developed in the laboratory to reinforce elastic fibers.
A) Scanning electron microscopy observation of the thermosensitive self-assembly of the synthetic elastic protein. B) Fluorescence optical microscopy observation of the synthetic elastic protein (red) added to the culture medium of cutis laxa fibroblasts (blue nuclei). The elastic fibers are evidenced by an anti-tropoelastin antibody coupled to a fluorescent dye (green). The synthetic elastic protein is actively integrated into the elastic fiber network (yellow). C) Fluorescence confocal microscopy observation of the endothelium (green) in zebrafish embryo. An extravasation of the synthetic elastic protein (red) is observed in the peri-endothelial zone 24h post-injection into the circulation (collaboration E. Lambert-Colloidal vectors and tissue transport research group).

Selection of publications  :

1. Moulin, L., Cenizo, V., Antu, A.N., Andre, V., Pain, S., Sommer, P. and Debret, R. Methylation of LOXL1 Promoter by DNMT3A in Aged Human Skin Fibroblasts. Rejuvenation Res 20 (2017) 103-110. PMID : 27396912. doi : 10.1089/rej.2016.1832.

2. Debret, R., Faye, C., Sohier, J. and Sommer, P. Brevet FR 16 54306, 13 Mai 2016 : Polypeptide dérivé de la tropoélastine et matériau biocompatible le comprenant.

3. Lorion, C., Faye, C., Maret, B., Trimaille, T., Regnier, T., Sommer, P. and Debret, R. Biosynthetic support based on dendritic poly(L-lysine) improves human skin fibroblasts attachment. J Biomater Sci Polym Ed 25 (2014) 136-149. PMID : 24116875. doi : 10.1080/09205063.2013.843966.

4. André, V., Béchetoille, N., Cenizo, V., Debret, R., Moulin, L. and Sommer, P. Brevet FR 2999926, 21 Décembre 2012 : Utilisations d’une substance inhibitrice de la méthylation de l’ADN pour stimuler la formation des fibres élastiques.

5. Debret, R., Cenizo, V., Aimond, G., Andre, V., Devillers, M., Rouvet, I., Megarbane, A., Damour, O. and Sommer, P. Epigenetic Silencing of Lysyl Oxidase-Like-1 through DNA Hypermethylation in an Autosomal Recessive Cutis Laxa Case. Journal of Investigative Dermatology 130 (2010) 2594-2601. PMID : 20613779. doi : 10.1038/jid.2010.186.

Collaborations  :

Pr. Gilles Faury, HP2 INSERM U1042, Grenoble.

Pr. Daniela Quaglino, Université de Modène et Reggio d’Emilie (UniMoRe), Modène, Italie.

Dr. Cyril Pailler-Mattéi, LTDS UMR5513 ECL/CNRS, Ecully.

Industrial partnerships : BASF-Beauty Care Solutions, ISIS PHARMA, Colcom.