Erik Schwartz

Responsive biomimetic networks from polyisocyanopeptide hydrogels

Mechanical responsiveness is essential to all biological systems down to the level of tissues and cells. The intra- and extracellular mechanics of such systems are governed by a series of proteins, such as microtubules, actin, intermediate filaments and collagen. As a general design motif, these proteins self-assemble into helical structures and superstructures that differ in diameter and persistence length to cover the full mechanical spectrum. Gels of cytoskeletal proteins display particular mechanical responses (stress stiffening) that until now have been absent in synthetic polymeric and low-molar-mass gels. Here we present synthetic gels that mimic in nearly all aspects gels prepared from intermediate filaments. They are prepared from polyisocyanopeptides grafted with oligo(ethylene glycol) side chains. These responsive polymers possess a stiff and helical architecture, and show a tunable thermal transition where the chains bundle together to generate transparent gels at extremely low concentrations. Using characterization techniques operating at different length scales (for example, macroscopic rheology, atomic force microscopy and molecular force spectroscopy) combined with an appropriate theoretical network model, we establish the hierarchical relationship between the bulk mechanical properties and the single-molecule parameters. Our results show that to develop artificial cytoskeletal or extracellular matrix mimics, the essential design parameters are not only the molecular stiffness, but also the extent of bundling. In contrast to the peptidic materials, our polyisocyanide polymers are readily modified, giving a starting point for functional biomimetic hydrogels with potentially a wide variety of applications, in particular in the biomedical field.

Helical poly(isocyanides): past, present and future

Stable helical polymers with a preferred handedness are compounds that offer intriguing characteristics. This review describes the progress in the synthesis of helical polyisocyanides and the investigations to determine their structural properties, such as helical pitch and handedness, by spectroscopic measurements and high resolution AFM. This review is not intended to be comprehensive; its purpose is to highlight recent studies that allow a better understanding of the main aspects of helical polyisocyanides.

The relationship between nanoscale architecture and charge transport in conjugated nanocrystals bridged by multichromophoric polymers

We report on the self-assembly and the electrical characterization of bicomponent films consisting of an organic semiconducting small molecule blended with a rigid polymeric scaffold functionalized in the side chains with monomeric units of the same molecule. The molecule and polymer are a perylene-bis(dicarboximide) monomer (M-PDI) and a perylene-bis(dicarboximide)-functionalized poly(isocyanopeptide) (P-PDI), which have been codeposited on SiO(x) and mica substrates from solution. These bicomponent films have been characterized by atomic force microscopy (AFM) and Kelvin probe force microscopy (KPFM), revealing the relationship between architecture and function for various supramolecular nanocrystalline arrangements at a nanometer spatial resolution. Monomer-polymer interactions can be controlled by varying solvent and/or substrate polarity, so that either the monomer packing dictates the polymer morphology or vice versa, leading to a morphology exhibiting M-PDI nanocrystals connected with each other by P-PDI polymer wires. Compared to pure M-PDI or P-PDI films, those bicomponent films that possess polymer interconnections between crystallites of the monomer display a significant improvement in electrical connectivity and a 2 orders of magnitude increase in charge carrier mobility within the film, as measured in thin film transistor (TFT) devices. Of a more fundamental interest, our technique allows the bridging of semiconducting crystals, without the formation of injection barriers at the connection points.

Post-modification of helical dipeptido polyisocyanides using the ‘click’ reaction

Polyisocyanopeptides have been synthesised containing acetylene groups on the side arms as scaffolds for multifunctional derivatisation by the copper-catalysed click reaction with a variety of azides. By using ethylene glycol azide and perylene azide chromophoric water-soluble polymeric nanowires (Mw 1–2 million Daltons) were formed. The potential to incorporate multiple chromophores was also demonstrated by the reaction of the acetylene-containing polymers with perylene azide and azidocoumarin dyes. In the latter case a blue-shifted emission of the coumarin was observed due to the interaction with the coupled perylene molecules. In particular the ability to form water-soluble dye-containing polymers, which can be modified by the addition of biomolecules, such as antibodies, proteins and peptides, give materials that are very promising as novel biomarker materials.

Macromolecular Scaffolding: The Relationship Between Nanoscale Architecture and Function in Multichromophoric Arrays for Organic Electronics

The optimization of the electronic properties of molecular materials based on optically or electrically active organic building blocks requires a fine-tuning of their self-assembly properties at surfaces. Such a fine-tuning can be obtained on a scale up to 10 nm by mastering principles of supramolecular chemistry, i.e., by using suitably designed molecules interacting via pre-programmed noncovalent forces. The control and fine-tuning on a greater length scale is more difficult and challenging. This Research News highlights recent results we obtained on a new class of macromolecules that possess a very rigid backbone and side chains that point away from this backbone. Each side chain contains an organic semiconducting moiety, whose position and electronic interaction with neighboring moieties are dictated by the central macromolecular scaffold. A combined experimental and theoretical approach has made it possible to unravel the physical and chemical properties of this system across multiple length scales. The (opto)electronic properties of the new functional architectures have been explored by constructing prototypes of field-effect transistors and solar cells, thereby providing direct insight into the relationship between architecture and function.

Synthesis, characterisation and chiroptical properties of ‘click’able polyisocyanopeptides

Rigid rod polyisocyanopeptides have been synthesised containing acetylene groups on the side arms as scaffolds for multifunctional derivatisation by the copper-catalysed click reaction between an acetylene and an azide. All materials were characterised in detail by spectroscopic procedures and for the processable polymers, atomic force microscopy was used to determine the molecular weight parameters. The solubility properties of the synthesised macromolecules are very dependent on the stereochemistry and/or the presence of solubilising trimethylsilyl groups on the acetylene function. The potential for derivatisation of the acetylene-containing materials using click chemistry was successfully demonstrated by the reaction of these polymers with aliphatic tails functionalised with azide moieties.

Disubstituted sialic acid ligands targeting siglecs CD33 and CD22 associated with myeloid leukaemias and B cell lymphomas

The siglec family of sialic acid-binding proteins are endocytic immune cell receptors that are recognized as potential targets for cell directed therapies. CD33 and CD22 are prototypical members and are validated candidates for targeting acute myeloid leukaemia and non-Hodgkins lymphomas due to their restricted expression on myeloid cells and B-cells, respectively. While nanoparticles decorated with high affinity siglec ligands represent an attractive platform for delivery of therapeutic agents to these cells, a lack of ligands with suitable affinity and/or selectivity has hampered progress. Herein we describe selective ligands for both of these siglecs, which when displayed on liposomal nanoparticles, can efficiently target the cells expressing them in peripheral human blood. Key to their identification was the development of a facile method for chemo-enzymatic synthesis of disubstituted sialic acid analogues, combined with iterative rounds of synthesis and rapid functional analysis using glycan microarrays.

Cysteine-containing polyisocyanides as versatile nanoplatforms for chromophoric and bioscaffolding.

The straightforward syntheses of polyisocyanides containing the alanine-cysteine motif in their side chains have been achieved. Detailed characterization of the polymers revealed a well-defined and highly stable helical conformation of the polyimine backbone responsible for the formation of rodlike structures of over one hundred nanometers. The 4(1) helix is further stabilized by beta-sheet-like interactions between the peptide arms. As a result, the cysteine sulfur atoms are regularly aligned along the polymer axis, which provides a unique platform for the scaffolding of various entities by using versatile click-chemistry postmodification approaches. For instance, pyrene derivatives were introduced through thio-specific reactions involving either maleimide, iodoacetamide, or thioester groups, leading to arrays of stacked chromophores with excimer-like emission. A water-soluble cysteine-rich polyisocyanide was successfully biotinylated and coupled to streptavidin.

Sequential energy and electron transfer in polyisocyanopeptide-based multichromophoric arrays.

We report on the synthesis and detailed photo-physical investigation of four model chromophore side chain polyisocyanopeptides: two homopolymers of platinum-porphyrin functionalized polyisocyanopeptides (Pt-porphyrin-PIC) and perylene-bis(dicarboximide) functionalized polyisocyanopeptides (PDI-PIC), and two statistical copolymers with different ratios of Pt-porphyrin and PDI molecules attached to a rigid, helical polyisocyanopeptide backbone. (1)H NMR and circular dichroism measurements confirm that our model compounds retain a chiral architecture in the presence of the chromophores. The combination of Pt-porphyrin and PDI chromophores allows charge- and/or energy transfer to happen. We observe the excitation and relaxation pathways for selective excitation of the Pt-porphyrin and PDI chromophores. Studies of photoluminescence and transient absorption on nanosecond and picosecond scales upon excitation of Pt-porphyrin chromophores in our multichromophoric assemblies show similar photophysical features to those of the Pt-porphyrin monomers. In contrast, excitation of perylene chromophores results in a series of energy and charge transfer processes with the Pt-porphyrin group and forms additional charge-transfer states, which behave as an intermediate state that facilitates electronic coupling in these multichromophoric systems.

Nanoscale Study of Polymer Dynamics

The thermal motion of polymer chains in a crowded environment is anisotropic and highly confined. Whereas theoretical and experimental progress has been made, typically only indirect evidence of polymer dynamics is obtained either from scattering or mechanical response. Toward a complete understanding of the complicated polymer dynamics in crowded media such as biological cells, it is of great importance to unravel the role of heterogeneity and molecular individualism. In the present work, we investigate the dynamics of synthetic polymers and the tube-like motion of individual chains using time-resolved fluorescence microscopy. A single fluorescently labeled polymer molecule is observed in a sea of unlabeled polymers, giving access to not only the dynamics of the probe chain itself but also to that of the surrounding network. We demonstrate that it is possible to extract the characteristic time constants and length scales in one experiment, providing a detailed understanding of polymer dynamics at the single chain level. The quantitative agreement with bulk rheology measurements is promising for using local probes to study heterogeneity in complex, crowded systems.