Post-translational modification of proteins is a strategy widely used in biological systems. It expands the diversity of the proteome and allows for tailoring of both the function and localization of proteins within cells as well as the material properties of structural proteins and matrices. Despite their ubiquity in biology, with a few exceptions, the potential of post-translational modifications in biomaterials synthesis has remained largely untapped. As a proof of concept to demonstrate the feasibility of creating a genetically encoded biohybrid material through post-translational modification, we report here the generation of a family of three stimulus-responsive hybrid materials-fatty-acid-modified elastin-like polypeptides-using a one-pot recombinant expression and post-translational lipidation methodology. These hybrid biomaterials contain an amphiphilic domain, composed of a β-sheet-forming peptide that is post-translationally functionalized with a C alkyl chain, fused to a thermally responsive elastin-like polypeptide. They exhibit temperature-triggered hierarchical self-assembly across multiple length scales with varied structure and material properties that can be controlled at the sequence level.
Inspired by biohybrid molecules that are synthesized in Nature through post-translational modification (PTM), we have exploited a eukaryotic PTM to recombinantly synthesize lipid-polypeptide hybrid materials. By co-expressing yeast N-myristoyltransferase with an elastin-like polypeptide (ELP) fused to a short recognition sequence in E. coli, we show robust and high yield modification of the ELP with myristic acid. The ELP’s reversible phase behavior is retained upon myristoylation and can be tuned to span a 30–60 °C. Myristoylated ELPs provide a versatile platform for genetically pre-programming self-assembly into micelles of varied size and shape. Their lipid cores can be loaded with hydrophobic small molecules by passive diffusion. Encapsulated doxorubicin and paclitaxel exhibit cytotoxic effects on 4T1 and PC3-luc cells, respectively, with potencies similar to chemically conjugated counterparts, and longer plasma circulation than free drug upon intravenous injection in mice.
Music therapy is gaining popularity as an intervention strategy for children with developmental disabilities, including autism spectrum disorder (ASD). This study was a pilot investigation of a classroom-based music-based intervention, Voices Together®, for improving communication skills in children with ASD and children with intellectual disabilities. Four local public elementary school special education classrooms, serving 5 children with a classification of autistic disorder and 32 children with intellectual disability without autism, were randomly selected to receive one of two levels of exposure to Voices Together music therapy: “long-term” (15 weeks beginning in January 2015 (Time 1), n = 14) or “short-term” (7 weeks beginning 7 weeks later in February (Time 2), n = 17). Using observational ratings, investigators reliably scored participants live in terms of their level of verbal responsiveness to prompts during three songs featured each week of the program. Both groups demonstrated increases in verbal responses over time; however, only the long-term group demonstrated significant within-group increases. Preliminary findings suggest that music therapy delivered in a classroom in 45-minute weekly sessions for 15 weeks can promote improvements in verbal responsiveness among individuals with autism and other developmental disabilities. Findings warrant further investigation into the efficacy of classroom-based music therapy programs.
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