by Keyword: Transforming growth factor beta1
Yuan, SC, Alvarez, Z, Lee, SR, Pavlovic, RZ, Yuan, CH, Singer, E, Weigand, SJ, Palmer, LC, Stupp, SI, (2024). Supramolecular Motion Enables Chondrogenic Bioactivity of a Cyclic Peptide Mimetic of Transforming Growth Factor-β1 Journal Of The American Chemical Society 146, 21555-21567
Transforming growth factor (TGF)-beta 1 is a multifunctional protein that is essential in many cellular processes that include fibrosis, inflammation, chondrogenesis, and cartilage repair. In particular, cartilage repair is important to avoid physical disability since this tissue does not have the inherent capacity to regenerate beyond full development. We report here on supramolecular coassemblies of two peptide amphiphile molecules, one containing a TGF-beta 1 mimetic peptide, and another which is one of two constitutional isomers lacking bioactivity. Using human articular chondrocytes, we investigated the bioactivity of the supramolecular copolymers of each isomer displaying either the previously reported linear form of the mimetic peptide or a novel cyclic analogue. Based on fluorescence depolarization and H-1 NMR spin-lattice relaxation times, we found that coassemblies containing the cyclic compound and the most dynamic isomer exhibited the highest intracellular TGF-beta 1 signaling and gene expression of cartilage extracellular matrix components. We conclude that control of supramolecular motion is emerging as an important factor in the binding of synthetic molecules to receptors that can be tuned through chemical structure.
JTD Keywords: Amphiphile, Cartilage, Chondrocytes, Chondrogenesis, Growth-factor-beta, Humans, Knee osteoarthritis, Neutralization, Peptides, cyclic, Progenitor cells, Repair, Scaffolds, Spectroscop, Tissue, Transforming growth factor beta1
Dhawan, U, Williams, JA, Windmill, JFC, Childs, P, Gonzalez-Garcia, C, Dalby, MJ, Salmeron-Sanchez, M, (2024). Engineered Surfaces That Promote Capture of Latent Proteins to Facilitate Integrin-Mediated Mechanical Activation of Growth Factors Advanced Materials 36, 2310789 
Conventional osteogenic platforms utilize active growth factors to repair bone defects that are extensive in size, but they can adversely affect patient health. Here, an unconventional osteogenic platform is reported that functions by promoting capture of inactive osteogenic growth factor molecules to the site of cell growth for subsequent integrin-mediated activation, using a recombinant fragment of latent transforming growth factor beta-binding protein-1 (rLTBP1). It is shown that rLTBP1 binds to the growth-factor- and integrin-binding domains of fibronectin on poly(ethyl acrylate) surfaces, which immobilizes rLTBP1 and promotes the binding of latency associated peptide (LAP), within which inactive transforming growth factor beta 1 (TGF-beta 1) is bound. rLTBP1 facilitates the interaction of LAP with integrin beta 1 and the subsequent mechanically driven release of TGF-beta 1 to stimulate canonical TGF-beta 1 signaling, activating osteogenic marker expression in vitro and complete regeneration of a critical-sized bone defect in vivo. An osteogenic platform that functions by capturing inactive growth factor molecules is engineered to overcome conventional challenges associated with the use of active growth factors. The platform triggers capture of inactive transforming growth factor beta-1 for its subsequent integrin-mediated activation which activates osteogenic downstream signaling in vitro and fully repairs critical-sized bone defect in vivo. image
JTD Keywords: Animals, Bone, Bone defect, Bone regeneration, Cell proliferation, Cells, Chemical activation, Defects, Differentiation, Fibronectin, Fibronectins, Growth factor, Growth factors, Humans, Integrin beta1, Integrins, Latency associated peptides, Latent tgf-beta binding proteins, Ltbp1, Osteogenesis, Osteogenic, Protein binding, Recombinant proteins, Release, Repair, Signal transduction, Surface properties, Tgf-beta, Tgf-β1, Transforming growth factor beta1, Transforming growth factors
