Mammalian Fuel Cells Produce Electric Current.

The increasing concern about climate change has led scientists around the world to develop clean energy technologies that may replace the traditional use of fossil fuels. A promising approach is the utilization of unicellular organisms as electron donors in bio-fuel cells. To date, this method has been limited to microorganisms such as bacteria, yeast, and microalgae.

Hydrogel Formation with Enzyme-Responsive Cyclic Peptides.

Self-assembling peptides (SAPs), which form hydrogels through physical cross-linking of soluble structures, are an intriguing class of materials that have been applied as tissue engineering scaffolds and drug delivery vehicles. For feasible application of these tissue mimetics via minimally invasive delivery, their bulk mechanical properties must be compatible with current delivery strategies. However, injectable SAPs which possess shear-thinning capacity, as well as the ability to reassemble after cessation of shearing can be technically challenging to generate.

pH-Responsive Charge-Conversion Progelator Peptides.

A simple strategy for generating stimuli-responsive peptide-based hydrogels charge-conversion of a self-assembling peptide (SAP) is described. These materials are formulated as soluble, polyanionic peptides, containing maleic acid, citraconic acid, or dimethylmaleic acid masking groups on each lysine residue, which do not form assemblies, but instead flow easily through high gauge needles and catheters. Acid-induced mask hydrolysis renews the zwitterionic nature of the peptides with concomitant and rapid self-assembly β-sheet formation into rehealable hydrogels.

Paclitaxel-terminated peptide brush polymers.

In this paper, we report the preparation of paclitaxel-terminated peptide brush polymers wherein cell uptake and toxicity are tunable based on peptide sequence. Synthesis was enabled using a new paclitaxel-containing chain termination agent for ring-opening metathesis polymerization (ROMP). Critically, reverse phase HPLC could be used to efficiently separate peptide brush polymers consisting of one fluorophore and one terminal paclitaxel from crude polymer mixtures.

Polymer brush hypersurface photolithography.

Polymer brush patterns have a central role in established and emerging research disciplines, from microarrays and smart surfaces to tissue engineering. The properties of these patterned surfaces are dependent on monomer composition, polymer height, and brush distribution across the surface. No current lithographic method, however, is capable of adjusting each of these variables independently and with micrometer-scale resolution.

Self-assembling peptides imaged by correlated liquid cell transmission electron microscopy and MALDI-imaging mass spectrometry.

We describe the observation of stimuli-induced peptide-based nanoscale assemblies by liquid cell transmission electron microscopy (LCTEM). LCTEM offers the opportunity to directly image nanoscale materials in liquid. Despite broad interest in characterizing biological phenomena, electron beam-induced damage remains a significant problem.

UV-responsive cyclic peptide progelator bioinks.

We describe cyclic peptide progelators which cleave in response to UV light to generate linearized peptides which then self-assemble into gel networks. Cyclic peptide progelators were synthesized, where the peptides were sterically constrained, but upon UV irradiation, predictable cleavage products were generated. Amino acid sequences and formulation conditions were altered to tune the mechanical properties of the resulting gels.

Enzyme-Induced Kinetic Control of Peptide-Polymer Micelle Morphology.

In this paper, experiment and simulation were combined to provide a view of the molecular rearrangements underlying the equilibrium and nonequilibrium transitions occurring in stimuli-responsive block copolymer amphiphile self-assemblies. Three block copolymer amphiphiles were prepared, each consisting of a hydrophilic peptide brush, responsive to proteolytic enzymes, and containing one of three possible hydrophobic blocks: (1) poly(ethyl acrylate), (2) poly(styrene), or (3) poly(lauryl acrylate). When assembled, they generate three spherical micelles each responsive to the addition of the bacterial protease, thermolysin.

Enzyme-responsive progelator cyclic peptides for minimally invasive delivery to the heart post-myocardial infarction.

Injectable biopolymer hydrogels have gained attention for use as scaffolds to promote cardiac function and prevent negative left ventricular (LV) remodeling post-myocardial infarction (MI). However, most hydrogels tested in preclinical studies are not candidates for minimally invasive catheter delivery due to excess material viscosity, rapid gelation times, and/or concerns regarding hemocompatibility and potential for embolism. We describe a platform technology for progelator materials formulated as sterically constrained cyclic peptides which flow freely for low resistance injection, and rapidly assemble into hydrogels when linearized by disease-associated enzymes.

Enzyme-Responsive Polymer Nanoparticles via Ring-Opening Metathesis Polymerization-Induced Self-Assembly.

Open-to-air aqueous-phase ring-opening metathesis polymerization-induced self-assembly (ROMPISA) is reported for forming well-defined peptide polymer nanoparticles at room temperature and with high solids concentrations (10 w/w%). For these materials, ROMPISA is shown to provide control over molecular weight with high conversion while open-to-air. Moreover, these peptide polymer nanoparticles can spontaneously rearrange into larger aggregate scaffolds in the presence of the proteolytic enzyme, thermolysin.

Micellar Thrombin-Binding Aptamers: Reversible Nanoscale Anticoagulants.

Aptamers are nucleic acid-based ligands that exhibit promising features including specific and reversible target binding and inhibition. Aptamers can function as anticoagulants if they are directed against enzymes of the coagulation cascade. However, they typically suffer from nucleolytic digestion and fast clearance from the bloodstream.

Biosynthetic Polymers as Functional Materials.

The synthesis of functional polymers encoded with biomolecules has been an extensive area of research for decades. As such, a diverse toolbox of polymerization techniques and bioconjugation methods has been developed. The greatest impact of this work has been in biomedicine and biotechnology, where fully synthetic and naturally derived biomolecules are used cooperatively.

Enzyme-Responsive Nanoparticles for Targeted Accumulation and Prolonged Retention in Heart Tissue after Myocardial Infarction.

A method for targeting to and retaining intravenously injected nanoparticles at the site of acute myocardial infarction in a rat model is described. Enzyme-responsive peptide-polymer amphiphiles are assembled as spherical micellar nanoparticles, and undergo a morphological transition from spherical-shaped, discrete materials to network-like assemblies when acted upon by matrix metalloproteinases (MMP-2 and MMP-9), which are up-regulated in heart tissue post-myocardial infarction.

Enzyme-directed assembly of nanoparticles in tumors monitored by in vivo whole animal imaging and ex vivo super-resolution fluorescence imaging.

Matrix metalloproteinase enzymes, overexpressed in HT-1080 human fibrocarcinoma tumors, were used to guide the accumulation and retention of an enzyme-responsive nanoparticle in a xenograft mouse model. The nanoparticles were prepared as micelles from amphiphilic block copolymers bearing a simple hydrophobic block and a hydrophilic peptide brush. The polymers were end-labeled with Alexa Fluor 647 dyes leading to the formation of labeled micelles upon dialysis of the polymers from DMSO/DMF to aqueous buffer.