Stiffness assisted cell-matrix remodeling trigger 3D mechanotransduction regulatory programs.

Autor: Kersey AL; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Cheng DY; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Deo KA; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Dubell CR; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Wang TC; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Jaiswal MK; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Kim MH; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Murali A; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Hargett SE; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Mallick S; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA; Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, Bryan, TX 77807, USA., Lele TP; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA., Singh I; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA; Department of Cell Biology and Genetics, School of Medicine, Texas A&M University, Bryan, TX 77807, USA; Interdisciplinary Program in Genetics, Texas A&M University, College Station, TX 77843, USA. Electronic address: isingh@tamu.edu., Gaharwar AK; Department of Biomedical Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA; Interdisciplinary Program in Genetics, Texas A&M University, College Station, TX 77843, USA; Center for Remote Health Technologies and Systems, Texas A&M University, College Station, TX 77843, USA; Department of Material Science and Engineering, College of Engineering, Texas A&M University, College Station, TX 77843, USA. Electronic address: gaharwar@tamu.edu.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2024 Apr; Vol. 306, pp. 122473. Date of Electronic Publication: 2024 Jan 18.
DOI: 10.1016/j.biomaterials.2024.122473
Abstrakt: Engineered matrices provide a valuable platform to understand the impact of biophysical factors on cellular behavior such as migration, proliferation, differentiation, and tissue remodeling, through mechanotransduction. While recent studies have identified some mechanisms of 3D mechanotransduction, there is still a critical knowledge gap in comprehending the interplay between 3D confinement, ECM properties, and cellular behavior. Specifically, the role of matrix stiffness in directing cellular fate in 3D microenvironment, independent of viscoelasticity, microstructure, and ligand density remains poorly understood. To address this gap, we designed a nanoparticle crosslinker to reinforce collagen-based hydrogels without altering their chemical composition, microstructure, viscoelasticity, and density of cell-adhesion ligand and utilized it to understand cellular dynamics. This crosslinking mechanism utilizes nanoparticles as crosslink epicenter, resulting in 10-fold increase in mechanical stiffness, without other changes. Human mesenchymal stem cells (hMSCs) encapsulated in 3D responded to mechanical stiffness by displaying circular morphology on soft hydrogels (5 kPa) and elongated morphology on stiff hydrogels (30 kPa). Stiff hydrogels facilitated the production and remodeling of nascent extracellular matrix (ECM) and activated mechanotransduction cascade. These changes were driven through intracellular PI3AKT signaling, regulation of epigenetic modifiers and activation of YAP/TAZ signaling. Overall, our study introduces a unique biomaterials platform to understand cell-ECM mechanotransduction in 3D for regenerative medicine as well as disease modelling.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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