Shaping polymersomes into predictable morphologies via out-of-equilibrium self-assembly.

Polymersomes are bilayer vesicles, self-assembled from amphiphilic block copolymers. They are versatile nanocapsules with adjustable properties, such as flexibility, permeability, size and functionality. However, so far no methodological approach to control their shape exists. Here we demonstrate a mechanistically fully understood procedure to precisely control polymersome shape via an out-of-equilibrium process. Carefully selecting osmotic pressure and permeability initiates controlled deflation, resulting in transient capsule shapes, followed by reinflation of the polymersomes. The shape transformation towards stomatocytes, bowl-shaped vesicles, was probed with magnetic birefringence, permitting us to stop the process at any intermediate shape in the phase diagram. Quantitative electron microscopy analysis of the different morphologies reveals that this shape transformation proceeds via a long-predicted hysteretic deflation-inflation trajectory, which can be understood in terms of bending energy. Because of the high degree of controllability and predictability, this study provides the design rules for accessing polymersomes with all possible different shapes.

Sensing cell adhesion using polydiacetylene-containing peptide amphiphile fibres.

Sensing cell adhesion by means of a colourimetric response provides an intuitive measure of cell binding. In this study polydiacetylene-containing peptide amphiphiles fibres were designed to sense cell adhesion by means of a colour change. The diacetylene-containing peptide amphiphiles were functionalised with the cell-binding motif RGDS, and subsequently mixed with non-functionalised diacetylene-containing spacer amphiphiles. The diacetylenes in the backbone of these fibres were polymerised using UV-light to give dark blue fibre solutions. Subsequent cell adhesion induced a colour change from blue to pink. The propensity of the RGDS fibres to change colour upon cell adhesion could be tuned by varying the C-terminal amino acid of the spacer amphiphile. In addition to this, by varying the RGDS density we found that the optimum colourimetric response was obtained for fibres with a 6 : 1 ratio of non-RGDS to RGDS amphiphiles.

Polymersome magneto-valves for reversible capture and release of nanoparticles.

Stomatocytes are polymersomes with an infolded bowl-shaped architecture. This internal cavity is connected to the outside environment via a small 'mouth' region. Stomatocytes are assembled from diamagnetic amphiphilic block-copolymers with a highly anisotropic magnetic susceptibility, which permits to magnetically align and deform the polymeric self-assemblies. Here we show the reversible opening and closing of the mouth region of stomatocytes in homogeneous magnetic fields. The control over the size of the opening yields magneto-responsive supramolecular valves that are able to reversibly capture and release cargo. Furthermore, the increase in the size of the opening is gradual and starts at fields below 10 T, which opens the possibility of using these structures for delivery and nanoreactor applications.

Cascade reactions in nanoreactors.

In an attempt to mimic the biosynthetic efficiencies of nature and in a search for greener, more sustainable alternatives to nowadays ways of producing chemicals, one-pot cascade reactions have attracted a lot of attention in the past decade. Since most catalysts are not compatible with each other, compartmentalization techniques have often been applied to prevent catalyst inactivation. A various array of nanoreactors have been developed to meet the demand of having a site-isolated catalyst system, while maintaining the catalyst activity. Both multienzyme nanoreactors as well as enzyme/metal catalyst or organocatalyst systems have shown great potential in one-pot cascade reactions and hold promise for future developments in this field.

Using viruses as nanomedicines.

The field of nanomedicine involves the design and fabrication of novel nanocarriers for the intracellular delivery of therapeutic cargo or for use in molecular diagnostics. Although traditionally recognized for their ability to invade and infect host cells, viruses and bacteriophages have been engineered over the past decade as highly promising molecular platforms for the targeted delivery and treatment of many human diseases. Inherently biodegradable, the outer capsids of viruses are composed entirely of protein building blocks, which can be genetically or chemically engineered with molecular imaging reagents, targeting ligands and therapeutic molecules. While there are several examples of viruses as in vitro molecular cargo carriers, their potential for applications in nanomedicine has only recently emerged. Here we highlight recent developments towards the design and engineering of viruses for the treatment of cancer, bacterial infections and immune system-related diseases.

Molecular tools for the construction of peptide-based materials.

Proteins and peptides are fundamental components of living systems where they play crucial roles at both functional and structural level. The versatile biological properties of these molecules make them interesting building blocks for the construction of bio-active and biocompatible materials. A variety of molecular tools can be used to fashion the peptides necessary for the assembly of these materials. In this tutorial review we shall describe five of the main techniques, namely solid phase peptide synthesis, native chemical ligation, Staudinger ligation, NCA polymerisation, and genetic engineering, that have been used to great effect for the construction of a host of peptide-based materials.

A structural study of the self-assembly of a palmitoyl peptide amphiphile.

Peptide amphiphiles consisting of a hydrophobic alkyl tail coupled to the eight-amino acid GANPNAAG have been studied extensively for their fibre forming properties. However, detailed characteristics of the fibre structure, such as peptide conformation and molecular organisation, are unknown to date. In this report a range of characterization techniques is described that have been employed to elucidate the internal structure of these fibres. Based on the results obtained by circular dichroism spectroscopy, X-ray diffraction and solid state NMR spectroscopy it was concluded that in a self-assembled state the peptide is in a stretched beta-sheet conformation, with the alkyl tails interdigitated and hydrogen-bonded along the axis of the fibre.

Enzymatic enantioselective C-C-bond formation in microreactors.

We have demonstrated that multiple crude enzyme lysates containing a hydroxynitrile lyase can be used for the enantioselective synthesis of cyanohydrins from aldehydes in microchannels. Using a microreactor setup, two important parameters were efficiently screened consuming only minute amounts of reagents. More importantly, results from the continuous flow reaction were fully consistent with results obtained from larger batchwise processes in which a stable emulsion was formed.

Elastin as a biomaterial for tissue engineering.

Biomaterials based upon elastin and elastin-derived molecules are increasingly investigated for their application in tissue engineering. This interest is fuelled by the remarkable properties of this structural protein, such as elasticity, self-assembly, long-term stability, and biological activity. Elastin can be applied in biomaterials in various forms, including insoluble elastin fibres, hydrolysed soluble elastin, recombinant tropoelastin (fragments), repeats of synthetic peptide sequences and as block copolymers of elastin, possibly in combination with other (bio)polymers. In this review, the properties of various elastin-based materials will be discussed, and their current and future applications evaluated.