Paul A Beales

• MPhys, PhD
• Professor (Associate) at University of Leeds

Understanding ion transport dynamics in reactive vesicles is pivotal for exploring biological and chemical processes and essential for designing synthetic cells. In this work, we investigate how proton transport and membrane potential regulate pH dynamics in an autocatalytic enzyme reaction within lipid vesicles. Combining experimental and numerica...

Hybrid membranes, consisting of phospholipids and amphiphilic block polymers, offer enhanced stability compared to liposomes and greater biocompatibility than polymersomes. These qualities make them a versatile platform for a wide range of applications across various fields. In this study, we have investigated the ability of solid-supported polymer...

Lipid nanoparticles have important applications as biomedical delivery platforms and broader engineering biology applications in artificial cell technologies. These emerging technologies often require changes in the shape and topology of biological or biomimetic membranes. Here we show that topologically‐active lyotropic liquid crystal nanoparticle...

We report the development of peptide-glycosaminoglycan hydrogels as injectable biomaterials for load-bearing soft tissue repair. The hydrogels are injectable as a liquid for clinical delivery, rapidly form a gel in situ, and mimic the osmotic swelling behaviour of natural tissue. We used a new in vitro model to demonstrate their application as a nu...

Pain, a complex and debilitating condition, necessitates innovative therapeutic strategies to alleviate suffering and enhance patients' quality of life. Vesicular systems hold the potential to enhance precision of drug localisation and release, prolong the duration of therapeutic action and mitigate adverse events associated with long-term pharmaco...

Lipid nanoparticles have important applications as biomedical delivery platforms and broader engineering biology applications in artificial cell technologies. These emerging technologies often require changes in the shape and topology of biological or biomimetic membranes. Here we show that topologically‐active lyotropic liquid crystal nanoparticle...

Background Postoperative pain following abdominal surgery is a significant obstacle to patient recovery, often necessitating high analgesic doses associated with adverse effects like cognitive impairment and cardiorespiratory depression. Reliable animal models are crucial for understanding the pathophysiology of post surgical pain and developing mo...

Enzymatic reactions that yield non-neutral products are known to involve feedback due to the bell-shaped pH-rate curve of the enzyme. Compartmentalizing the reaction has been shown to lead to transport-driven oscillations in theory; however, there have been few reproducible experimental examples. Our objective was to determine how the conditions co...

Hybrid vesicles consisting of natural phospholipids and synthetic amphiphilic copolymers have shown remarkable material properties and potential for biotechnology, combining the robustness of polymers with the biocompatibility of phospholipid membranes. To predict and optimize the mixing behavior of lipids and copolymers, as well as understand the...

Self-assembling peptides are a promising biomaterial with potential applications in medical devices and drug delivery. In the right combination of conditions, self-assembling peptides can form self-supporting hydrogels. Here, we describe how balancing attractive and repulsive intermolecular forces is critical for successful hydrogel formation. Elec...

Hybrid vesicles consisting of natural phospholipids and synthetic amphiphilic copoly- mers have shown remarkable material properties and potential for biotechnology, com- bining the robustness of polymers with the biocompatibility of phospholipid mem- branes. To predict and optimize the mixing behavior of lipids and copolymers, as well as understan...

Hybrid vesicles consisting of natural phospholipids and synthetic amphiphilic copoly- mers have shown remarkable material properties and potential for biotechnology, com- bining the robustness of polymers with the biocompatibility of phospholipid mem- branes. To predict and optimize the mixing behavior of lipids and copolymers, as well as understan...

Self-assembling peptides are a promising biomaterial with potential applications in medical de-vices and drug delivery. In the right combination of conditions, self-assembling peptides can form self-supporting hydrogels. Here, we describe how balancing attractive and repulsive intermo-lecular forces is critical for successful hydrogel formation. El...

Hybrid vesicles consisting of phospholipids and block‐copolymers are increasingly finding applications in science and technology. Herein, small angle X‐ray scattering (SAXS) and cryo‐electron tomography (cryo‐ET) are used to obtain detailed structural information about hybrid vesicles with different ratios of 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosp...

Membrane fusion is a tool to increase the complexity of model membrane systems. Here, we use silica nanoparticles to fuse liquid-disordered DOPC giant unilamellar vesicles (GUVs) and liquid-ordered DPPC:Cholesterol (7:3) GUVs. After fusion, GUVs display large membrane domains as confirmed by fluorescence confocal microscopy. Laurdan spectral imagin...

Hybrid vesicles consisting of phospholipids and block-copolymers are increasingly finding applications in science and technology. Herein, small angle X-ray scattering (SAXS) and cryo-electron tomography (cryo-ET) were used to obtain detailed structural information about hybrid vesicles with different ratios of 1-palmitoyl-2-oleoyl-sn-glycero-3-phos...

Membrane fusion is a tool to increase the complexity of model membrane systems. Here, we use silica nanoparticles to fuse liquid-disordered DOPC giant GUVs and liquid-ordered DPPC:Cholesterol (7:3) GUVs. After fusion, GUVs display large membrane domains as confirmed by fluorescence confocal microscopy. Laurdan spectral imaging of the membrane phase...

The use of nanoparticles (NPs) for biomedical applications implies their delivery into the organism where they encounter biological fluids. In such biological fluids, proteins and other biomolecules adhere to the surface of the NPs forming a biomolecular corona that can alter significantly the behaviour of the nanomaterials. Here, we investigate th...

A self-avoiding walk (SAW) is a sequence of moves on a grid that does not visit the same point more than once. SAWs are used to study how networks form, including social networks, biological networks and computer networks, and have provided inspiration to scientists, artists and designers. Here we describe a collaborative project which aims to deli...

This article charts the development of a collaboration between poet Dr Caitlin Stobie and scientist Dr Paul Beales, resulting from their partnership in the Leeds Creative Labs: Bragg Edition. The authors show their motivations for working together and the philosophical conversations that developed as they discussed artificial life, synthetic matter...

Hybrid vesicles (HVs) that consist of mixtures of block copolymers and lipids are robust biomimetics of liposomes, providing a valuable building block in bionanotechnology, catalysis, and synthetic biology. However, functionalization of HVs with membrane proteins remains laborious and expensive, creating a significant current challenge in the field...

We investigate the impact of a bovine serum albumin corona on interactions between silica nanoparticles (SNPs) of two different sizes and giant lipid vesicles. The protein corona alters the morphological response of vesicles to SNPs, demonstrating that a protein corona can change the interaction mechanism between nanoparticles and lipid membranes.

Lipid nanoparticles have important applications as biomedical delivery platforms and broader engineering biology applications in artificial cell technologies. These emerging technologies often require changes in the shape and topology of biological or biomimetic membranes. Here we show that topologically-active lyotropic liquid crystal nanoparticle...

The transmission of chemical signals via an extracellular solution plays a vital role in collective behavior in cellular biological systems and may be exploited in applications of lipid vesicles such as drug delivery. Here, we investigated chemical communication in synthetic micro- and nanovesicles containing urease in a solution of urea and acid....

Back pain affects a person's health and mobility as well as being associated with large health and social costs. Lower back pain is frequently caused by degeneration of the intervertebral disc. Current operative and non-operative treatments are often ineffective and expensive. Nucleus augmentation is designed to be a minimally invasive method of re...

Lipids and block copolymers can individually self-assemble into vesicles, each with their own particular benefits and limitations. Combining polymers with lipids allows for further optimisation of the vesicle membranes for bionanotechnology applications. Here, POPC lipid is mixed with poly(1,2-butadiene-block-ethylene oxide) of two different molecu...

Lipids and block copolymers can individually self-assemble into vesicles, each with their own particular benefits and limitations. Combining polymers with lipids allows for further optimisation of the vesicle membranes for bionanotechnology applications. Here, POPC lipid is mixed with poly(1,2-butadiene-block-ethylene oxide) of two different molecu...

Lipids and block copolymers can individually self-assemble into vesicles, each with their own particular benefits and limitations. Combining polymers with lipids allows for further optimisation of the vesicle membranes for bionanotechnology applications. Here, POPC lipid is mixed with poly(1,2-butadiene-block-ethylene oxide) of two different molecu...

Hybrid vesicles (HVs) that consist of mixtures of block copolymers and lipids are robust biomimetics of liposomes, providing a valuable building block in bionanotechnology, catalysis and synthetic biology. However, functionalisation of HVs remains laborious and expensive, creating a significant current challenge in the field. Here, using a new appr...

Hybrid vesicles (HVs) that consist of mixtures of block copolymers and lipids are robust biomimetics of liposomes, providing a valuable building block in bionanotechnology, catalysis and synthetic biology. However, functionalisation of HVs remains laborious and expensive, creating a significant current challenge in the field. Here, using a new appr...

p>There is a growing demand to develop smart nanomaterials that are structure-responsive as they have the potential to offer enhanced dose, temporal and spatial control of compounds and chemical processes. The naturally occurring pH gradients found throughout the body make pH an attractive stimulus for guiding the response of a nanocarrier to speci...

Insect pests are a major cause of crop losses worldwide, with an estimated economic cost of $470 billion annually. Biotechnological tools have been introduced to control such insects without the need for chemical pesticides; for instance, the development of transgenic plants harbouring genes encoding insecticidal proteins. The Vip3 (vegetative inse...

Self‐assembling hydrogels are promising materials for regenerative medicine and tissue engineering. However, designing hydrogels that replicate the 3–4 order of magnitude variation in soft tissue mechanics remains a major challenge. Here hybrid hydrogels are investigated formed from short self‐assembling β‐fibril peptides, and the glycosaminoglycan...

Membrane fusion is a key process to develop new technologies in synthetic biology, where artificial cells function as biomimetic chemical microreactors. Fusion events in living cells are intricate phenomena that require the coordinate action of multicomponent protein complexes. However, simpler synthetic tools to control membrane fusion in artifici...

Hypothesis The properties of stable gold (Au) nanoparticle dispersions can be tuned to alter their activity towards biomembrane models. Experiments Au nanoparticle coating techniques together with rapid electrochemical screens of a phospholipid layer on fabricated mercury (Hg) on platinum (Pt) electrode have been used to moderate the phospholipid l...

Fibroblast growth factor receptor 3 (FGFR3) is a transmembrane tyrosine kinase protein in the fibroblast growth factor receptor family, which plays a key role in many biological processes. Over-expression and activating mutations in FGFR3 are frequent in non-invasive bladder cancer, highlighting this protein as a potential biomarker for recurrent b...

The endosomal sorting complex required for transport (ESCRT) organises in supramolecular structures on the surface of lipid bilayers to drive membrane invagination and scission of intraluminal vesicles (ILVs), a process also controlled by membrane mechanics. However, ESCRT association with the membrane is also mediated by electrostatic interactions...

Investigative systems for purified membrane transporters are almost exclusively reliant on the use of phospholipid vesicles or liposomes. Liposomes provide an environment to support protein function; however, they also have numerous drawbacks and should not be considered as a “one-size fits all” system. The use of artificial vesicles comprising blo...

The endosomal sorting complex required for transport (ESCRT) organises in supramolecular structures on the surface of lipid bilayers to drive membrane invagination and scission of intraluminal vesicles (ILVs), a process also controlled by membrane mechanics. However, ESCRT association with the membrane is also mediated by electrostatic interactions...

Sterilisation and preservation of vesicle formulations are important considerations for their viable manufacture for industry applications, particular those intended for medicinal use. Here, we undertake an initial investigation of the stability of hybrid lipid-block copolymer vesicles to common sterilisation and preservation processes, with partic...

Sterilisation and preservation of vesicle formulations are an important consideration for their viable manufacture for industry applications, particular those intended for medicinal use. Here we undertake an initial investigation of the stability of hybrid lipid – block copolymer vesicles to common sterilisation and preservation processes, with par...

The anticipated benefits of nano-formulations for drug delivery are well known: for nanomedicines to achieve this potential, new materials are required with predictive and tuneable properties. Excretion of excipients following delivery is advantageous to minimise the possibility of adverse effects; biodegradability to non-toxic products is therefor...

Silver nanoparticles (AgNPs) have wide-ranging applications, including as additives in consumer products and in medical diagnostics and therapy. Therefore understanding how AgNPs interact with biological systems is important for ascertaining any potential health risks due to the likelihood of high levels of human exposure. Besides any severe, acute...

Silver nanoparticles (AgNPs) have wide-ranging applications, including as additives in consumer products and in medical diagnostics and therapy. Therefore understanding how AgNPs interact with biological systems is important for ascertaining any potential health risks due to the likelihood of high levels of human exposure. Besides any severe, acute...

p>The anticipated benefits of nano-formulations for drug delivery are well known: for nanomedicines to achieve this potential, new materials are required with predictive and tuneable properties. Excretion of excipients following delivery is advantageous to minimise the possibility of adverse effects; biodegradability to non-toxic products is theref...

Artificial cells can shed new light on the molecular basis for life and hold potential for new chemical technologies. Inspired by how nature dynamically regulates its membrane compartments, we aim to repurpose the endosomal sorting complex required for transport (ESCRT) to generate complex membrane architectures as suitable scaffolds for artificial...

Impact statement: Artificial membranes with complex topography aid the understanding of biological processes where membrane geometry plays a key regulatory role. In this review, we highlight how emerging material and engineering technologies have been employed to create minimal models of cell signaling pathways, in vitro. These artificial systems...

Artificial cells can shed new light on the molecular basis for life and hold potential for new chemical technologies. Inspired by how nature dynamically regulates its membrane compartments, we aim to repurpose the endosomal sorting complex required for transport (ESCRT) to generate complex membrane architectures as suitable scaffolds for artificial...

Impact statement: The timing and rate of release of pharmaceuticals from advanced drug delivery systems is an important property that has received considerable attention in the scientific literature. Broadly, these mostly fall into two classes: controlled release with a prolonged release rate or triggered release where the drug is rapidly released...

The complexity of eukaryotic cells is underscored by the compartmentalization of chemical signals by phospholipid membranes. A grand challenge of synthetic biology is building life from the ‘bottom-up’, for the purpose of generating systems simple enough to precisely interrogate biological pathways or for adapting biology to perform entirely novel...

The concept of compartmentalization in artificial cell research was the focus of a Royal Society Theo Murphy meeting at the Kavli Royal Society Centre, Chichelely Hall in Buckinghamshire, UK, 26–27 February 2018.

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of e...

Hybrid vesicles composed of lipids and block copolymers hold promise for increasing liposome stability and providing a stable environment for membrane proteins. Recently we reported the successful functional reconstitution of the integral membrane protein cytochrome bo3 (ubiquinol oxidase) into hybrid vesicles composed of a blend of phospholipids a...

A combination of standard fluorescence microscopy and flow cytometry offers a practical new approach to study encounter rates and preferences during various live cell membrane signalling events.

The application of membrane proteins in biotechnology requires robust, durable reconstitution systems that enhance their stability and support their functionality in a range of working environments. Vesicular architectures are highly desirable to provide the compartmentalisation to utilise the functional transmembrane transport and signalling prope...

The full capabilities of membrane proteins in bionanotechnology can only be realised through improvements in their reconstitution environments that combine biocompatibility to support function and durability for long term stability. We demonstrate that hybrid vesicles composed of natural phospholipids and synthetic diblock copolymers have the poten...

Lipid nanodiscs have broad applications in membrane protein assays, biotechnology and materials science. Chemical modification of the nanodiscs to expand their functional attributes is generally desirable for all of these uses. We present a method for site-selective labelling of the N-terminus of the nanodisc's membrane scaffold protein (MSP) using...

Degeneration of the spinal discs is a major cause of back pain. During the degeneration process, there is a loss of glycosaminoglycans (GAGs) from the proteoglycan-rich gel in the disc's nucleus, which adversely alters biomechanical performance. Current surgical treatments for back pain are highly invasive and have low success rates; there is an ur...

Polybia-MP1 (MP1) is a bioactive host-defense peptide with known anticancer properties. Its activity is attributed to excess serine (phosphatidylserine (PS)) on the outer leaflet of cancer cells. Recently, higher quantities of phosphatidylethanolamine (PE) were also found at these cells' surface. We investigate the interaction of MP1 with model mem...

This issue presents a themed collection on investigating, harnessing and mimicking biological compartmentalisation using in vitro model systems, where biophysical mechanisms and biomembrane engineering are essential for realisation of the potential of membrane-bound compartments.

Compartmentalisation of cellular processes is fundamental to regulation of metabolism in Eukaryotic organisms and is primarily provided by membrane-bound organelles. These organelles are dynamic structures whose membrane barriers are continually shaped, remodelled and scaffolded by a rich variety of highly sophisticated protein complexes. Towards t...

We present optical observations of phase separation in mixed model membranes in the form of giant unilamellar vesicles. These observations are compared to the phase behavior of lipid mixtures, which we determined by X-ray scattering and differential scanning calorimetry or extracted from the existing literature. The domain properties are affected n...

Although the molecular mechanisms underlying the pathology of amyloidoses are not well understood, the interaction between amyloid proteins and cell membranes is thought to play a role in several amyloid diseases. Amyloid fibrils of β2-microglobulin (β2m), associated with dialysis-related amyloidosis (DRA), have been shown to cause disruption of an...

Recently a new class of materials emerged with the assembly of DNA-coated phospholipid nanodiscs into columnar BioNanoStacks. Within these stacks, lipid discs are periodically incorporated, resulting into quasi one dimensional superstructures. With each disc surrounded by two recombinant scaffolding proteins, we decided to examine whether the poly-...

The release of cytochrome c (cyt c) from mitochondria is an important early step during cellular apoptosis, however the precise mechanism by which the outer mitochondrial membrane becomes permeable to these proteins is as yet unclear. Inspired by our previous observation of cyt c crossing the membrane barrier of giant unilamellar vesicle model syst...

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The release of cytochrome c from mitochondria is a key signaling mechanism in apoptosis. Although extramitochondrial proteins are thought to initiate this release, the exact mechanisms remain unclear. Cytochrome c (cyt c) binds to and penetrates lipid structures containing the inner mitochondrial membrane lipid cardiolipin (CL), leading to protein...

We demonstrate the self-organization of quasi-one-dimensional nanostructures with periodic features using nature's primary three building blocks: lipids, DNA, and proteins. The periodicity of these "BioNanoStacks" is controllable through selection of the length of the DNA spacers. We show that BioNanoStacks can be reversibly assembled and disassemb...

We investigate the effect of serum albumin on the interaction of ZnO nanoparticles with DOPC lipid membranes and show that the size-stabilizing effect of the protein corona enhances their interaction with lipid membranes, which manifests, in part, as an increased ordering in the lipid packing.

We present a critical review of recent work related to the assembly of multicompartment liposomes clusters using nucleic acids as a specific recognition unit to link liposomal modules. The asymmetry in nucleic acid binding to its non-self complementary strand allows the controlled association of different compartmental modules into composite system...

Understanding the interactions between nanoparticles (NPs) and biological matter is a high-priority research area because of the importance of elucidating the physical mechanisms underlying the interactions leading to NP potential toxicity as well as NP viability as therapeutic vectors in nanomedicine. Here, we use two model membrane systems, giant...

The design of novel, soft membrane structures with chemical and physical properties that are tunable across a broad spectrum of parameter space is important for the development of new functional materials. Many potential applications of these novel membranes will likely require biocompatible interfaces, e.g., for functional reconstitution of integr...

We present a novel platform for investigating the composition-specific interactions of proteins (or other biologically relevant molecules) with model membranes composed of compositionally distinct domains. We focus on the interaction between a mitochondrial-specific lipid, cardiolipin (CL), and a peripheral membrane protein, cytochrome c (cyt c). W...

Phospholipid nanodiscs are a rare form of stable lipid self-assembly. The discs are formed by allowing lipids to self-assemble in the presence of membrane scaffold proteins (MSP). Each disc contains two MSP, wrapping around the edge of a leaflet of the bilayer. Although nanodiscs have become an important and versatile tool among model membrane syst...

Asymmetric building blocks afford assembly of more complex, sophisticated materials than their homogeneous counterparts. Phase separation of mixed membranes produces asymmetric surface textures in lipidvesicles. Membranes that demix into coexisting liquid phases ripen such that the vesicle domain morphology exhibits a Janus-like texture. DNA is com...

Lipids and block copolymers can be individually assembled into unsupported, spherical membranes (liposomes or polymersomes), each having their own particular benefits and limitations. Here we demonstrate the preparation of microscale, hybrid "lipopolymersomes" composed of the common lipid POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine)...

The partitioning of different cholesterol-modified single-stranded DNA molecules (chol-DNAs) between the domains of phase-separated lipid vesicles is investigated by laser-scanning confocal fluorescence microscopy. All chol-DNAs studied preferentially localized into the fluid phase of giant vesicles in liquid-solid phase coexistence (1:1 DLPC:DPPC,...

We use membrane-anchored DNA as model adhesion receptors between lipid vesicles. By studying the thermal stability of DNA duplex formation, which tethers the vesicles into superstructures, we show that the melting temperature of a 10-base DNA sequence is dependent on the lipid composition of the tethered vesicles. We propose a simple model that des...

Many important signaling processes occur in the interactions between lipid organelles: a multitude of ligands and receptors are localized to the surface of lipid structures and vary in many ways, including their length and the strength of their interactions. DNA strands with hydrophobic modifications anchor to the surface of lipid membranes. These...

A number of elaborate liposome systems and theories based on fluid phospholipid membranes have been investigated and their synthetic analogue, amphiphilic diblock copolymers have provided an alternative to phospholipids as mimics of the cell membrane with the unique morphology and a variety of tunable properties. Though phospholipids can afford lot...

Nature employs lipid structures as a smart, environment-sensitive packaging material that also acts as a two dimensional solvent for proteins, receptors and channels to interact at the interface between these compartments. Even simple vesicles reconstituted in vitro with minimal lipid components can exhibit a zoology of morphological changes, phase...

Both phospholipid vesicles and their more stable and versatile block-copolymer synthetic analogs have captured significant attention in recent years for their use in fundamental membrane studies and for their potential use in biomimetic and engineering applications. By taking advantage of biological molecular tethers (e.g., DNA hybridization or rec...

We demonstrate a method of heterogeneous vesicle binding using membrane-anchored, single-stranded DNA that can be used over several orders of magnitude in vesicle size, as demonstrated for large 100 nm vesicles and giant vesicles several microns in diameter. The aggregation behavior is studied for a range of DNA surface concentrations and solution...

Lipids are biological amphiphiles that, in aqueous solution, self-assemble into a variety of structures, including bilayer membranes that form hollow vesicles. In membranes with two or more constituents, lipids are well-mixed when the temperature is sufficiently high. As the temperature is lowered, systems undergo ordering transitions, membranes ph...

In multi-component lipid membranes, phase separation can lead to the formation of domains. The morphology of fluid-like domains has been rationalized in terms of membrane elasticity and line tension. We show that the morphology of solid-like domains is governed by different physics, and instead reflects the molecular ordering of the lipids. An unde...

Giant lipid vesicles are important, optically-resolvable, model systems for studying physical phenomena in biomembranes and have important applications as technological containers in the engineering of novel soft materials. Giant vesicles containing two different lipid components are well-mixed in the fluid phase; as the temperature is lowered phas...

We study model membranes in the form of giant unilamellar vesicles (GUVs) composed of two saturated lipids with different hydrophilic headgroups or different hydrophobic chain lengths. Lateral phase separation in the lipid bilayer causes solid-like 'gel' domains to nucleate and grow in the fluid membrane. We study the shape and size of these domain...

We studied the crystallization of lysozyme solutions by adding sodium chloride at pH = 4.5, 5.9 and 7.8. A universal crystallization boundary is found if data are scaled according to the salt concentration normalized by the square of the charge at the appropriate pH. Calculations show that this finding is consistent with recent attempts to rational...