Biological membranes play an essential role in living organisms by providing stable and functional compartments, preserving cell architecture, whilst supporting signalling and selective transport that are mediated by a variety of proteins embedded in the membrane. However, mimicking cell membranes – to be applied in artificial systems – is very challenging because of the vast complexity of biological structures. In this respect a highly promising strategy to designing multifunctional hybrid materials/systems is to combine biological molecules with polymer membranes or to design membranes with intrinsic stimuli-responsive properties. Here we present supramolecular polymer assemblies resulting from self-assembly of mostly amphiphilic copolymers either as 3D compartments (polymersomes, PICsomes, peptosomes), or as planar membranes (free-standing films, solid-supported membranes, membrane-mimetic brushes). In a bioinspired strategy, such synthetic assemblies decorated with biomolecules by insertion/encapsulation/attachment, serve for development of multifunctional systems. In addition, when the assemblies are stimuli-responsive, their architecture and properties change in the presence of stimuli, and release a cargo or allow “on demand” a specific in situ reaction. Relevant examples are included for an overview of bioinspired polymer compartments with nanometre sizes and membranes as candidates in applications ranging from drug delivery systems, up to artificial organelles, or active surfaces. Both the advantages of using polymer supramolecular assemblies and their present limitations are included to serve as a basis for future improvements.

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Bioinspired polymer vesicles and membranes for biological and medical applications

Catalysis by small molecules (≤1000 Da, 10−9 m) that are capable of binding and activating substrates through attractive, noncovalent interactions has emerged as an important approach in organic and organometallic chemistry. While the canonical noncovalent interactions, including hydrogen bonding, ion pairing, and π stacking, have become mainstays of catalyst design, the cation–π interaction has been comparatively underutilized in this context since its discovery in the 1980s. However, like a hydrogen bond, the cation–π interaction exhibits a typical binding affinity of several kcal mol−1 with substantial directionality. These properties render it attractive as a design element for the development of small-molecule catalysts, and in recent years, the catalysis community has begun to take advantage of these features, drawing inspiration from pioneering research in molecular recognition and structural biology. This Review surveys the burgeoning application of the cation–π interaction in catalysis.

The Cation–π Interaction in Small-Molecule Catalysis

Polymersomes as synthetic analogues of liposomes appear frequently in relevant literature as promising candidates for a wide range of different applications including drug delivery, theranostic multitools, and nanoreactors. In particular, as nanotransporters for nanomedical applications in vivo, requirements concerning the reproducible manufacturing and reliable size control are extremely high. This Perspective highlights the importance of size control especially in the context of nanomedicine and gives an overview of the theoretical background of amphiphilic self-assembly leading to different preparation methods, where their feasibility of controlling polymersomes’ size is discussed.

Techniques To Control Polymersome Size

The field of biomimicry is embracing the construction of complex assemblies that imitate both biological structure and function Advancements in the design of these mimetics have generated a growing vision for creating an artificial cell or protocell Polymersomes are vesicles that can be made from synthetic, biological, or hybrid polymers and can be used as a model template to build cell-like structures In this perspective, we discuss various areas where polymersomes have been used to mimic cell functions as well as areas in which the synthetic flexibility of polymersomes would make them ideal candidates for a biomembrane mimetic Designing a polymersome that comprehensively displays the behaviors discussed herein has the potential to lead to the development of an autonomous, responsive particle that resembles the intelligence of a biological cell

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Engineering Polymersome Protocells.

Liposomes have been widely applied as carriers of molecules in the fields of nanodevices, drug delivery and gene delivery, as well as a mimic for cell membranes. In the biosensor field, liposomes find special application in signal amplification, due to their excellent carrier properties for encapsulation of signal marker compounds across a wide spectrum of sensing modalities. Additionally, the ability to modify the liposome surface structure to perform recognition functions with a wide range of types of analytes is an important aspect of their use in bioanalysis. This article provides an extensive review of the utility of liposomes in the fields of biosensor and bioanalysis with a focus on these two aspects. The aspects related to the translation of liposomes into commercially viable devices for biosensing are also discussed, and the hurdles to more widespread deployment in point of care systems are addressed.

Liposomes in biosensors

Vesicles from Pluronic L121 (PEO5-PPO68-PEO5) triblock copolymers were first stabilized by a permanent interpenetrating polymer network and then gently immobilized onto a glass or mica surface. Fluorescence-labeled micrometer-sized vesicles were visualized with confocal laser scanning microscopy, and smaller sized capsules, around 100 nm, were probed by liquid atomic force microscopy. The immobilized vesicles were weakly attached to a negatively charged surface via negatively charged polyelectrolytes in combination with Mg2+ ions and can be reversibly detached from the surface by slightly elevated temperatures. To illustrate that the immobilized vesicles remain responsive to external stimuli, we show that it is possible to transform their shape from spherical to cylindrical by introducing a second Pluronic, namely, P123 (PEO20-PPO70-PEO20). The detailed transition process has been recorded in real time by confocal laser scanning microscopy. Electron microscopy studies confirmed that a similar morphology change also occurs in the bulk.

Gentle immobilization of nonionic polymersomes on solid substrates.

Vesicles from Pluronic L121 (PEO5−PPO68−PEO5) triblock copolymers were stabilized by an interpenetrating polymer network from pentaerythritol tetraacrylate by UV or thermal initiator induced radical polymerization. Fluorescence labeling, atomic force microscopy, and electron microscopy studies were used to study the morphology of the particles and showed that stable vesicles are formed. The block copolymers are noncovalently trapped in the interpenetrating polyacrylate network. The stabilized vesicles retain their size for more than 1 month at room temperature. Upon cooling, the vesicles reversibly lose block copolymer.

Stabilization of Polymersome Vesicles by an Interpenetrating Polymer Network

Vesicles from Pluronic L121 (PEO5-PPO68-PEO5) triblock copolymers were stabilized against aggregation by Pluronic P85 (PEO26-PPO40-PEO26) micelles. Both the vesicles and the micelles were reinforced by an interpenetrating polymer network from pentaerythritol tetraacrylate (PETA). AFM, electron microscopy and fluorescence labeling studies are used to investigate the morphology of the capsules. The P85 micelles are integrated into the L121 polymersome walls, while both types of Pluronic block copolymer are also non-covalently trapped in their respective interpenetrating acrylate networks. The micelle-containing vesicles retain their size upon heating until at least 33 °C. Upon cooling below room temperature the vesicles reversibly lose block copolymers. It was shown that the double-stabilized vesicles are readily internalized in HeLa and Caco-2 cells.

Pluronic polymersomes stabilized by core cross-linked polymer micelles

Small unilamellar vesicles are formed spontaneously by simple mixing of lamellae-forming diblock copolymer PB10PE10 (PB is a butylene oxide block, and PE an ethylene oxide block) with micelle-forming diblock copolymer PB10PE18. Small angle neutron scattering (SANS) measurements show that the average vesicle radius may be as small as 30 nm with a polydispersity index of 0.15. From the SANS measurements it can also be deduced that the vesicles have a 3.4 nm thick hydrophobic membrane core and a 1.2 nm hydrophilic corona. Furthermore, it is seen that the vesicles coexist with spherical micelles. The influence of the mixing ratio as well as the concentration of the polymeric components is studied. Results of the micelle size, the vesicle size and the shell structure are confirmed by cryo-TEM measurements.

Small monodisperse unilamellar vesicles from binary copolymer mixtures

Trigger the block: Stable biocompatible protein polymersomes can be generated by a triggered templated self-assembly route (see picture). Pluronic L121 vesicles (red core with blue corona) take up a biosynthetic triblock copolymer CSXSXC into their unilamellar shell. In response to changes in pH (trigger), the S block becomes hydrophobic and adapts to the template vesicle, thus directing the formation of protein polymersomes.

Frans A. M. Leermakers

Papers

Gentle immobilization of nonionic polymersomes on solid substrates.

Stabilization of Polymersome Vesicles by an Interpenetrating Polymer Network

Pluronic polymersomes stabilized by core cross-linked polymer micelles

Small monodisperse unilamellar vesicles from binary copolymer mixtures

Triggered Templated Assembly of Protein Polymersomes