Mechanotransduction and Stiffness-Sensing: Mechanisms and Opportunities to Control Multiple Molecular Aspects of Cell Phenotype as a Design Cornerstone of Cell-Instructive Biomaterials for Articular Cartilage Repair

• Published in: International journal of molecular sciences Vol. 21; no. 15; p. 5399
• Main Authors: Selig, Mischa, Lauer, Jasmin C, Hart, Melanie L, Rolauffs, Bernd
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.07.2020; MDPI
• Subjects: Adhesion; Angiogenesis; articular cartilage; beta Catenin - genetics; beta Catenin - metabolism; Binding sites; Biocompatible Materials - chemistry; Biocompatible Materials - therapeutic use; Biomarkers - metabolism; Biomaterials; Biomechanics; Biomedical materials; Cartilage; Cartilage (articular); Cartilage, Articular - drug effects; Cartilage, Articular - immunology; Cartilage, Articular - pathology; Cartilage, Articular - surgery; Cell cycle; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cell surface; chondrocyte; Chondrocytes; Chondrocytes - cytology; Chondrocytes - drug effects; Chondrocytes - metabolism; Chondrogenesis - drug effects; Chondrogenesis - genetics; Collagen; Collagen (type II); Collagen Type II - genetics; Collagen Type II - metabolism; Composition; Cytoskeleton; Differentiation; Gene expression; Gene Expression Regulation; Genotype & phenotype; Growth factors; Hardness - physiology; Humans; IL-1β; Interleukin 1; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Kinases; Mechanotransduction; Mechanotransduction, Cellular - genetics; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; mesenchymal stromal cells (MSCs); Mesenchyme; osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - immunology; Osteoarthritis - surgery; Osteoarthritis - therapy; Phenotype; Phenotypes; Proteins; Regeneration - drug effects; Regeneration - genetics; Repair; Review; SOX9 Transcription Factor - genetics; SOX9 Transcription Factor - metabolism; Stiffness; stiffness sensing; Traction force; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; articular cartilage; immunomodulation; cell shape; mechanotransduction; osteoarthritis; mesenchymal stromal cells (MSCs); RhoA/Rho associated protein kinase (ROCK); re-differentiation; Rho-GTPases; β-catenin; clinical; de-differentiation; chondrocyte; SRY-related HMG box gene 9 (SOX9); TGF-β; stiffness sensing; biomaterials; α-catenin; Wnt; cartilage repair; phenotype modulation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21155399

Since material stiffness controls many cell functions, we reviewed the currently available knowledge on stiffness sensing and elucidated what is known in the context of clinical and experimental articular cartilage (AC) repair. Remarkably, no stiffness information on the various biomaterials for clinical AC repair was accessible. Using mRNA expression profiles and morphology as surrogate markers of stiffness-related effects, we deduced that the various clinically available biomaterials control chondrocyte (CH) phenotype well, but not to equal extents, and only in non-degenerative settings. Ample evidence demonstrates that multiple molecular aspects of CH and mesenchymal stromal cell (MSC) phenotype are susceptible to material stiffness, because proliferation, migration, lineage determination, shape, cytoskeletal properties, expression profiles, cell surface receptor composition, integrin subunit expression, and nuclear shape and composition of CHs and/or MSCs are stiffness-regulated. Moreover, material stiffness modulates MSC immuno-modulatory and angiogenic properties, transforming growth factor beta 1 (TGF-β1)-induced lineage determination, and CH re-differentiation/de-differentiation, collagen type II fragment production, and TGF-β1- and interleukin 1 beta (IL-1β)-induced changes in cell stiffness and traction force. We then integrated the available molecular signaling data into a stiffness-regulated CH phenotype model. Overall, we recommend using material stiffness for controlling cell phenotype, as this would be a promising design cornerstone for novel future-oriented, cell-instructive biomaterials for clinical high-quality AC repair tissue.