Handan Acar

Self-assembled template-directed synthesis of one-dimensional silica and titania nanostructures.

Mineralized biological materials such as shells, skeleton, and teeth experience biomineralization. Biomimetic materials exploit the biomineralization process to form functional organic-inorganic hybrid nanostructures. In this work, we mimicked the biomineralization process by the de novo design of an amyloid-like peptide that self-assembles into nanofibers. Chemically active groups enhancing the affinity for metal ions were used to accumulate silicon and titanium precursors on the organic template. The self-assembly process and template effect were characterized by CD, FT-IR, UV-vis, fluorescence, rheology, TGA, SEM, and TEM. The self-assembled organic nanostructures were exploited as a template to form high-aspect-ratio 1-D silica and titania nanostructures by the addition of appropriate precursors. Herein, a new bottom-up approach was demonstrated to form silica and titania nanostructures that can yield wide opportunities to produce high-aspect-ratio inorganic nanostructures with high surface areas. The materials developed in this work have vast potential in the fields of catalysis and electronic materials.

Self-assembled one-dimensional soft nanostructures

The self-assembly process is a bottom-up approach and is the spontaneous aggregation of many different subunits into well-defined functional structures with varying properties. Self-assembly is an attractive method to develop one-dimensional nanostructures and is controlled by many factors including temperature, pH and electrolyte addition. Novel self-assembled one-dimensional nanostructures are finding applications in regenerative medicine and electronics as well as in fabrication of nanoscale electronic, mechanic, magnetic, optical, and combinatorial devices. Their utility comes from their high ratio of surface area to volume, and their quantum-confinement effects. This paper reviews one-dimensional self-assembled organic nanostructures classified according to the non-covalent forces acting on their formation.

Self-assembled peptide nanofiber templated one-dimensional gold nanostructures exhibiting resistive switching.

An amyloid-like peptide molecule self-assembling into one-dimensional nanofiber structure in ethanol was designed and synthesized with functional groups that can bind to gold ions. The peptide nanofibers were used as templates for nucleation and growth of one-dimensional gold nanostructures in the presence of ascorbic acid as reducing agent. We performed multistep seed-mediated synthesis of gold nanoparticles by changing peptide/gold precursor and peptide/reducing agent ratios. Gold nanostructures with a wide range of morphologies such as smooth nanowires, noodle-like one-dimensional nanostructures, and uniform aggregates of spherical nanoparticles were synthesized by use of an environmentally friendly synthesis method. Nanoscale electrical properties of gold-peptide nanofibers were investigated using atomic force microscopy. Bias dependent current (IV) measurements on thin films of gold-peptide nanofiber hybrid revealed tunneling dominated transport and resistive switching. Gold-peptide nanofiber composite nanostructures can provide insight into electrical conduction in biomolecular/inorganic composites, highlighting their potential applications in electronics and optics.

Self-assembling peptide-based building blocks in medical applications ☆

Abstract Peptides and peptide‐conjugates, comprising natural and synthetic building blocks, are an increasingly popular class of biomaterials. Self‐assembled nanostructures based on peptides and peptide‐conjugates offer advantages such as precise selectivity and multifunctionality that can address challenges and limitations in the clinic. In this review article, we discuss recent developments in the design and self‐assembly of various nanomaterials based on peptides and peptide‐conjugates for medical applications, and categorize them into two themes based on the driving forces of molecular self‐assembly. First, we present the self‐assembled nanostructures driven by the supramolecular interactions between the peptides, with or without the presence of conjugates. The studies where nanoassembly is driven by the interactions between the conjugates of peptide‐conjugates are then presented. Particular emphasis is given to in vivo studies focusing on therapeutics, diagnostics, immune modulation and regenerative medicine. Finally, challenges and future perspectives are presented. Graphical abstract Figure. No Caption available.

Template-directed synthesis of silica nanotubes for explosive detection.

Fluorescent porous organic-inorganic thin films are of interest of explosive detection because of their vapor phase fluorescence quenching property. In this work, we synthesized fluorescent silica nanotubes using a biomineralization process through self-assembled peptidic nanostructures. We designed and synthesized an amyloid-like peptide self-assembling into nanofibers to be used as a template for silica nanotube formation. The amine groups on the peptide nanofibrous system were used for nucleation of silica nanostructures. Silica nanotubes were used to prepare highly porous surfaces, and they were doped with a fluorescent dye by physical adsorption for explosive sensing. These porous surfaces exhibited fast, sensitive, and highly selective fluorescence quenching against nitro-explosive vapors. The materials developed in this work have vast potential in sensing applications due to enhanced surface area.

Amyloid-like peptide nanofiber templated titania nanostructures as dye sensitized solar cell anodic materials

One-dimensional titania nanostructures can serve as a support for light absorbing molecules and result in an improvement in the short circuit current (Jsc) and open circuit voltage (Voc) as a nanostructured and high-surface-area material in dye-sensitized solar cells. Here, self-assembled amyloid-like peptide nanofibers were exploited as an organic template for the growth of one-dimensional titania nanostructures. Nanostructured titania layers were utilized as anodic materials in dye sensitized solar cells (DSSCs). The photovoltaic performance of the DSSC devices was assessed and an enhancement in the overall cell performance compared to unstructured titania was observed.

Transient Biocompatible Polymeric Platforms for Long-Term Controlled Release of Therapeutic Proteins and Vaccines

Polymer-based interpenetrating networks (IPNs) with controllable and programmable degradation and release kinetics enable unique opportunities for physisorption and controlled release of therapeutic proteins or vaccines while their chemical and structural integrities are conserved. This paper presents materials, a simple preparation method, and release kinetics of a series of long-term programmable, biocompatible, and biodegradable polymer-based IPN controlled release platforms. Release kinetics of the gp41 protein was controlled over a 30-day period via tuning and altering the chemical structure of the IPN platforms. Post-release analysis confirmed structural conservation of the gp41 protein throughout the process. Cell viability assay confirmed biocompatibility and non-cytotoxicity of the IPNs.

Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein-protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are two major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a Förster resonance energy transfer (FRET)-based tracking system. Using this platform, we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.

Peptides in immunoengineering

Abstract The immune system plays a critical role in our health. When functioning correctly, the immune system continually protects us from the most common to the most deadly and mysterious maladies: common influenza to HIV and cancer. When functioning incorrectly, autoimmune diseases such as diabetes and multiple sclerosis ensue. Understanding how the immune system functions and learning how to rationally control it to protect against or treat disease has been a challenge historically burdened by the immunology and medical fields. Recently, exciting strides in immunological discoveries and investigational tools have allowed outsiders to enter the fold, chief among them being the biomaterials field. With biomaterials as an engineering tool, rational manipulation of the immune system at the cellular and molecular levels has expanded, shedding new light on the functioning of the immune system while also showing promising preclinical and clinical data for more effective and safer treatments. As a flourishing subset of the biomaterials field, peptides have been used as a major design component of the immune engineering strategy. Peptides, because of their chemically defined nature, engineerability, and range of complexity, provide useful functionalities when designing strategies for vaccination, cancer immunotherapy, and the treatment of autoimmune disorders. This chapter will examine the peptide-based strategies for immune modulation in detail and discuss the promise and outstanding challenges facing the field of immune engineering.

Antifouling Properties of a Self-Assembling Glutamic Acid-Lysine Zwitterionic Polymer Surface Coating

There is a need for the development of antifouling materials to resist adsorption of biomacromolecules. Here we describe the preparation of a novel zwitterionic block copolymer with the potential to prevent or delay the formation of microbial biofilms. The block copolymer comprised a zwitterionic (hydrophilic) section of alternating glutamic acid (negatively charged) and lysine (positively charged) units and a hydrophobic polystyrene section. Cryo-TEM and dynamic-light-scattering (DLS) results showed that, on average, the block copolymer self-assembled into 7-nm-diameter micelles in aqueous solutions (0 to 100 mM NaCl, pH 6). Quartz crystal microbalance with dissipation monitoring (QCM-D), atomic force microscopy (AFM), and contact angle measurements demonstrated that the block copolymer self-assembled into a brush-like monolayer on polystyrene surfaces. The brush-like monolayer produced from a 100 mg/L block copolymer solution exhibited an average distance, d, of approximately 4-8 nm between each block copolymer molecule (center to center). Once the brush-like monolayer self-assembled, it reduced EPS adsorption onto the polystyrene surface by ∼70% (mass), reduced the rate of bacterial attachment by >80%, and inhibited the development of thick biofilms. QCM-D results revealed that the EPS molecules penetrate between the chains of the brush and adsorb onto the polystyrene surface. Additionally, AFM analyses showed that the brush-like monolayer prevents the adhesion of large (> d) hydrophilic colloids onto the surface via hydration repulsion; however, molecules or colloids small enough to fit between the brush polymers (< d) were able to be adsorbed onto the surface via van der Waals interactions. Overall, we found that the penetration of extracellular organelles, as well as biopolymers through the brush, is critical for the failure of the antifouling coating, and likely could be prevented through tuning of the brush density. Stability and biofilm development testing on multiple surfaces (polypropylene, glass, and stainless steel) support practical applications of this novel block copolymer.