Chemical compartmentalisation by membranes: from biological mechanism to biomimetic applications

Biological cells maintain their complex network of chemical reactions by spatially confining individual pathways into distinct compartments. These compartments are delimited by highly dynamic phospholipid membranes, which regulate the bidirectional transport and sorting of cargo. Nature has developed membranes not merely as passive barriers for segregation of materials but it has equipped them with selective channels that allow sophisticated molecular translocation and signalling, and machineries that remodel the membrane to generate nanovessels for materials' transport.

Physical scientists have developed methods to reconstitute some of these functional interfaces and compartments in vitro, whether they are membranes composed of natural lipids, or biomimetic self-assembled membranes constructed from block copolymers or polyelectrolytes. These model systems facilitate greater understanding of membrane interactions and processes, but also hold great promise for the development of new biomimetic chemical technologies in areas such as drug delivery, nanoreactors and biosensors. Ultimately, the greatest challenge is to engineer functional model membrane systems to enable the creation of a truly artificial cell. In recent years, great strides have been made in the bottom-up assembly of membrane-encapsulated systems with increasing complexity and functionality. This topical themed issue on “Chemical compartmentalisation by membranes: from biological function to biomimetic application” presents a collection of research and perspectives into understanding, mimicking and harnessing biological compartmentalisation using in vitro model systems, where biophysical understanding and biomembrane engineering hold equal significance for realisation of the potential applications of membrane-bound compartments. Compartmentalisation comes in different flavours, whether it is biological or synthetic machineries shaping the membrane, or the membranes themselves that are recreated synthetically, for example for the controlled-release of encapsulated materials.

In this issue, we review the biophysical literature on protein-mediated membrane remodelling processes, such as fission, fusion and protrusion, in reconstituted lipid membrane models (DOI: 10.1039/C5CP00480B) and present our perspective on how these protein-induced deformations and topological transitions might be applied in the generation of synthetic model cells. Our review aims to inspire further efforts in the design of bio-inspired tools that can sculpt membranes and can be employed for the construction of minimal cell-like systems.

Two articles in this themed issue address membrane remodelling and specificity of protein–membrane interactions as key events in disease development. Firstly, Vanni et al. (DOI: 10.1039/C5CP00244C) present work on the binding specificity to membranes of α-synuclein, which is thought to be a key nucleation event in the formation of toxic protein fibrils in Parkinson's disease. From their findings, they suggest a generic property of membranes composed of methyl-branched lipids as highly adhesive substrates for peripheral proteins that bind through hydrophobic interactions. Secondly, Baumgart and co-workers (DOI: 10.1039/C4CP05883F) investigate membrane remodelling processes induced by α-synuclein. They demonstrate an area expansion of the membrane due to α-synuclein, which they propose thins the bilayer and eventually leads to tubulation or fragmentation of the membrane. The authors suggest that these membrane remodelling events may be important in supporting α-synuclein's role in vesicle trafficking processes, offering a different perspective for interpretation of the role of this protein in neurodegeneration.

Saša Svetina and colleagues (DOI: 10.1039/C5CP01243K) expand our understanding of single protein–membrane interactions to describe whole organelle behaviour. They use theoretical approaches to investigate mechanical and molecular aspects of the yeast nuclear envelope shape changes during cell division. They propose a model to explain the observed symmetry of the nuclear shapes by showing that the nuclear envelope has analogous mechanical properties to lipid vesicles, and that forces exerted by the chromosomes clustered at the spindle pole bodies on the extending nuclear membrane maintain the nuclear envelope shape.

Membrane remodelling need not be induced by biomolecules; the marriage of biological and synthetic components is a key focus in developing novel applications through hybrid materials in Synthetic Biology. A detailed study by de Planque et al. (DOI: 10.1039/C4CP05882H) looks at the ability of silica nanoparticles, to behave as membrane disruptors. Silica nanoparticles are candidate drug delivery systems that can have cytotoxic effect by inducing cell membrane damage. The authors show that the surface chemistry of native silica provides a very strong membrane interaction motif. Also in this issue, remodelling of the membrane through poration events is explored by Ryadnov and co-workers (DOI: 10.1039/C5CP01185J), who investigate synthetic amphiphiles that have similar antibacterial properties to host defence peptides. They demonstrate that supramolecular micellar assemblies of these amphiphiles have promising selectivity for tuneable targeting to biological membranes.

Of course, engineering the membranes themselves is a different approach for creating model compartmentalisation systems. Palivan and colleagues (DOI: 10.1039/C4CP05879H) create biomimetic polymer vesicles (polymersomes) made selectively permeable to ions through reconstitution of bacterial ionophores within these membranes. Intriguingly, ion transport by the ionophores in these systems is shown to be functional despite the polymer membrane being greater than twice the thickness of a natural lipid bilayer.

Membrane adhesion is an important process for communication between membrane-bound compartments. Gordon and co-workers (DOI: 10.1039/C4CP05876C) present a perspective highlighting the subtleties and complexities of the coupling between membrane adhesion processes and lipid phase separation, which facilitates the formation of distinct two-dimensional compartments on the membrane surface. Furthermore, this group presents some of their original research on this topic (DOI: 10.1039/C4CP05877A), which demonstrates that when homogeneous fluid membranes close to a phase de-mixing transition bind to a surface-supported membrane through specific biotin–avidin interactions, two types of membrane heterogeneity form in the adhesion sites that are compositionally distinct from the non-adherent membrane: a receptor-deficient ordered lipid phase and a receptor-enriched disordered lipid phase. Interestingly, the authors note that the topologies of these domains in these contact zones show similarities to structures formed in the immune synapse.

Cicuta et al. (DOI: 10.1039/C5CP01340B) further investigate membrane adhesion processes using synthetic DNA “receptors”, which are attached to the membrane in single-stranded form and bind their complementary strand on the target membrane. DNA-functionalised lipid vesicles adhere to surface supported membranes through Watson–Crick base-pairing interactions. These authors quantify the membrane tension induced by this adhesion process and the thermal melting of the DNA linkers. This latter process is described by a statistical mechanical model, which semi-quantitatively describes the experimental data with a single parameter fit, demonstrating the validity of their theoretical approach.

A significant application of membrane-bound compartments is their use in the delivery of bioactive molecules. Webb et al. (DOI: 10.1039/C4CP05872K) create lipid vesicle–magnetic nanoparticle composite materials and demonstrate that magnetic fields can be used to trigger the release of biomacromolecules that are encapsulated within the lipid vesicle compartments. Furthermore, Zasadzinski and co-workers (DOI: 10.1039/C4CP05881J) present a method to encapsulate copper sulphide nanoparticles inside PEGylated liposomes. They demonstrate that permeabilisation of the lipid bilayer can be triggered by near infra-red light.

Encapsulation of complex biological processes and parallel reactions is one of the challenges towards building minimal functional cell-like systems. Staniland and Bain (DOI: 10.1039/C5CP00375J) introduce us to a relatively new function of compartmentalisation: as a ‘shaper’ of inorganic materials. They present a perspective on the biomineralisation of inorganic nanoparticles inside vesicle compartments, mimicking processes that occur within magnetotactic bacteria. The spatial organisation of biological processes in living cells also inspires Ces et al. (DOI: 10.1039/C4CP05933F) to demonstrate isolation of biological processes within multicompartment vesicles, where transcription and translation of two different proteins from DNA plasmids are isolated within different compartments of these architectures.

It is evident from the breadth of contributions to this themed issue how the diversity of approaches enriches the vibrancy of current research into the understanding and application of biomimetic compartments constructed from self-organised membranes. We hope this themed issue will be a useful resource for scientists active in the area of membrane compartmentalisation but also inspire scientists from a wide range of specialities to contribute to ongoing efforts in what is an exciting and challenging multidisciplinary research area.

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