Amphiphiles are molecules that contain both hydrophilic and hydrophilic parts and depending on their ratio, they can assemble in water into either spherical or cylindrical micelles or membranes (controlled by the dimensionless packing factor). Membranes are a critical component of biological organisation and natural amphiphiles (phospholipids) set the limits within and between cells. Membranes have the necessity to avoid contact between their edges and water and this drives their deformation to form enclosed structures known as vesicles typically spherical to minimise surface area. Amphiphiles can be made using block copolymers which comprise hydrophilic and hydrophobic polymers joined together. The macromolecular nature of the copolymers imposes two unique features to amphiphilic copolymer membranes: (i) hydrophobic entanglement and (ii) hydrophilic brush-like configuration. This makes copolymer vesicles also known as polymersomes very different from their low molecular counterparts. Entanglement (for low Tg polymers) means high mechanical deformability and toughness, whilst the brush like configuration enables to surround the polymer- some with a dense hydrophilic layer that controls both colloidal stability and interaction with its environment. Relevant publications:The necessary and sufficient condition to form polymersomes is that amphiphilic copolymers have the appropriate hydrophilic/hydrophobic ratio to form membranes. These have a conformation as showed in the figure on the right-hand side, where the hydrophobic chains come together to form a bilayer and the hydrophilic chains extend from the interface to the water. The macromolecular nature of the copolymers imposes two unique features to polymersomes membrane: hydrophobic entanglement and hydrophilic brush-like configuration. This makes polymersomes very different from the low molecular counterparts. Entanglement (for low Tg polymers) means high mechanical deformability and toughness, whilst the brush like configuration enables to surround the polymersome with a dense hydrophilic layer that controls both colloidal stability and interaction with its environment.
- A. Blanazs, J. Madsen, G. Battaglia, A. J. Ryan and S. P. Armes Mechanistic Insights For Block Copolymers Morphologies: How Do Worms Form Vesicles? J. Am. Chem. Soc. 2011 133 (41), 16581–16587
- T. Smart, O. Mykhaylyk, A. J. Ryan, and G. Battaglia* Polymersomes hydrophilic corona scaling relations Soft Matter 2009, 5, 3607 - 3610
- C. Fernyhough, A. J. Ryan, and G. Battaglia pH controlled assembly of a polybutadiene–poly(methacrylic acid) copolymer in water: packing considerations and kinetic limitations. Soft Matter 2009, 5, 1674 – 1682
- C. Lo Presti, M. Massignani, T. Smart, H. Lomas, and G. Battaglia Polymersomes: nature inspired nanometer sized compartments, J. Mater. Chem. 2009 19, 3576 – 3590
- G. Battaglia and A.J. Ryan Bilayers and Interdigitation in Block Copolymer Vesicles, J. Am. Chem. Soc. 2005, 127, 8757-8764
(a) Cubic micellar phase formed by poly(ethylene oxide)-poly(ethyl ethylene) in an epoxy network. (b) Hexagonally packed cylinders formed by poly(ethylene oxide)-poly(butadiene) in water. (c) Disordered lamel- lar phase formed by poly(styrene)-block-poly(butadiene)-block-poly-(methyl methacrylate) in an epoxy network. (d) Disordered network formed by poly(ethylene oxide)-poly(butadiene) in water. (e) Hexagonally packed vesi- cles formed by poly(ethylene oxide)-poly(butylene oxide) in water. (f) Im3m bicontinuous phase formed by poly(ethylene oxide)-poly(butylene oxide) in water (Figure adapted from Smart et al. Nano Today, 2008, 3, 38–46)
The vesicle is the simplest structure that membranes can enclose into and it is typically an isotropic phase formed at low concentration of amphiphiles in water. Vesicles can be formed with size ranging from 50nm to 500μm with the smaller size vesicles being colloidally more stable. At higher amphiphile con- centration, vesicles aggregate into vesicular gels either dispersed as clusters or into connected very loose gels. At concentrations close to 50% in volume of water, the amphiphiles assemble into long-range ordered structures with the sponge phase being the most common at the intermediate concentration, amphiphiles form lamellae and at high concentrations, inversed hexagonal and cubic structure are often encountered. Some of these phases are showed in the Figure above with amphiphilic copolymers forming differ- ent structures either in water or other selective solvents. We have been studying these phase transition and map out the phase diagrams for copolymers in water to direct future work on structural materials as well as to inform on the mechanism of polymersome formation
- T. Smart, A. J. Ryan, J. Howse,and G. Battaglia, Homopolymer induced aggregation of polymersomes Langmuir, 2010, 26 (10), pp 7425–7430
- T. Smart, C. Fernyhough, A. J. Ryan, G. Battaglia Controlling Fusion and Aggregation in Polymersome
Dispersions Macromol. Rapid Commun. 2008, 29, 1855-1860
- G. Battaglia and A.J. Ryan Effect of amphiphile size on the transformation from a lyotropic gel to a vesicular dispersion, Macromolecules 2006, 39, 798-805
- G. Battaglia and A.J. Ryan The evolution of vesicles from bulk lamellar gels, Nature Mater. 2005, 4,
Topological engineering of polymersomes
(Shape topology) By controlling the way polymersome enclose we can engineer their shape ac- cessing to archicteure such as sphere, tubes, and high-genus structures including simple and complex toroids. (Surface topology) the mixture of different copolymers on the same polymersomes allows to control pattern and cluster formation tuning copolymer/copolymer interaction
Polymersomes can be formed using either bottom-up or top- down approaches. The former involves a total solubilisation of the membrane-forming copolymers typically us- ing organic solvents or exploiting pH, temperature or other stimuli that control the copolymer solubility. Once dissolved, the solution conditions are changed (e.g. solvent exchange of environmental changes) so to makes the copolymer amphiphilic and hence triggering the self-assembling. Polymersomes requires a minimum radius to be stable and hence a number of aggregates in order of thousands. This means that at the early stages of self-assembly, membrane forming copolymers nucleate into frustrated micelles and they further grow into enclosed vesicles. Similarly, as we hydrate a given amphiphilic copolymers, its internal structure evolve according to the different phase diagram discussed above and the final size and shape of the vesicles is given by the kinetics of hydration. We have been studying these kinetic for several years and learned how to control both bottom-up or top-down approaches to engineering the polymersome shape topology as showed in the Figure above. On a different level of complexity, we can also engineer the polymersome surface topology by combining different polymersome-forming copolymers and, in doing so, tuning the interaction between them. The resulting structures can be as simple as phase-separated bimodal or spinodal domains or more complex super-symmetric arrangements. Similarly, the same approach can be used to control the polymersome topography mixing different size copolymers and controlling line tension. Finally, the asymmetry of the polymersome can be further controlled pushing the phase separations to full coarsening (see the structure showed in Figure above).
- L. Ruiz-Perez, L. Messager, J. Gaitzsch, A. Joseph, L. Sutto, F. L. Gervasio and G. Battaglia Molecular engineering of polymersome surface topology Science Adv. 2016, e1500948
- L. Ruiz-Perez, J. Madsen, E. Themistou, J. Gaitzsch, L. Messanger, S. Armes and G.Battaglia Nanoscale detection of metal -labeled copolymers in patchy polymersomes Polymer Chem. 2015, 6, 2065-2068
- J.D Robertson, G. Yealland, M .Avila-Olias, L. Chierico, O. Bandman, S. A. Renshaw ,G. Battaglia pHsensitive tubular polymersomes: formation and applications in cellular delivery ACS Nano, 2014, 8, 4650–4661
- R. Pearson, N. Warren, A. Lewis, S. P. Armes and G. Battaglia pH and temperature effect on PMPC - PDPA copolymer self-assembly Macromolecules, 2013, 46, 1400–1407
- G. Battaglia, C. LoPresti, S. Forster M. Massignani, J. Madsen, N. J. Warren, S. P. Armes, C. Vasilev, J. K. Hobbs, S. Chirasatitsin, A. Engler Wet nano-scale imaging and testing of polymersomes Small 2011, 7, (14), 2010–2015
- C.LoPresti, M.Massignani, C.Fernyhough, A.Blanazs, A.J.Ryan, J.Madsen, N.J.Warren, S.P.Armes, A.L. Lewis S. Chirasatitsin, A. Engler, G. Battaglia* Controlling polymersomes surface topology at the nanoscale by membrane confined polymer/polymer phase separation ACS Nano 2011, 5 (3),1775–1784
- G. Battaglia and A.J. Ryan Pathways of polymeric vesicle formation, J. Phys. Chem. B 2006, 110 10272- 10279.
- G. Battaglia and A.J. Ryan Neuron-Like Tubular Membranes Made of Diblock Copolymer Amphiphiles, Angew. Chem. Int. Ed. 2006, 45, 2052-2056
3D Interface engineering
Surface patterning is a key feature of materials science that requires the design of complex structures. Surface topographical features have often been generated through ‘top-down’ strategies using micro-contact printing or by electron beam-, photo-, or dip pen lithography. These techniques provide control over size and arrangement in the micro- and nano- scales with remarkable reproducibility. However, the need for patterned surfaces has extended its niche from the electronics industry to surface chemistry, protein biology, biosensors, and even cell biomechanics. For biological applications ,in particular, surface engineering has dominated recent biomaterials design and shown how specific surface functionalities are cell adhesive, for example, carboxyl, amine, or hydroxide groups. The topological arrangement of such chemistries has an equally important effect; the order of nanoscale surface roughness can control and direct cell functions. While several efforts highlight how nanoscale topological properties influence cells, most of these studies have been limited to two-dimensional (2D) systems. Three-dimensional (3D) materials often present uniform surface chemistry via surface immobilization or direct cross-linking of a binding motif to the scaffold, yielding either homogeneous or protein polymer hydrogels. We have thus created a unique approach to control surface chemistry and topology exploiting interface-confined events. We engineer the interface by choosing/synthesising copolymers that preferentially sit at a given interface whether this is a liquid/liquid or air/liquid. This is combined with appropriate molecular engineering allowing us to ensure physical and/or chemical anchoring with the resulting materials having surface properties entirely controlled one block of the copolymer (See figure 1). Furthermore, these can be chosen to interact between each other allowing the design of specific patterns and topologies ( see figures 2 and 3). We have showed this using both the combination of high internal phase emulsion (HIPE) templating with interface confined block copolymer self-assembly to engineer 3D porous nano-functionalised materials as scaffolds for cell culture (Figure 2) and electro-spinning of mixture of homopolymer A with diblock AB, where the B component segregates at the air/liquid interface upon solvent evaporation during the spinning process (see figures 1 and 3).
- P. Viswanathan, M. Ondeck, S. Chirasatitsin, K. Nghamkham, D. Cecchin, G. C. Reilly, A. J. Engler* and G. Battaglia* 3D Surface Topology Guides Stem Cell Adhesion and Differentiation Biomaterials 2015, 52, 140–147
- P. Viswanathan ,E. Themistou, K. Ngamkham, G. Reilly, S. Armes, G. Battaglia Controlling Surface Topology and Functionality of Electrospun Fibers using Amphiphilic Block Copolymers to Direct Mesenchymal Progenitor Cell Adhesion Biomacromolecules 2015, 16(1):66-75
- P. Viswanathan, D. Johnson, C. Hurley, N. Cameron and G. Battaglia* 3D Surface Functionalization of Emulsion-templated Polymeric Foams Macromolecules 2014, 47, 7091–7098
- P. Viswanathan, S. Chirasatitsin, K. Ngamkham, A. Engler, and G. Battaglia*, Cell instructive microporous scaffolds through interface engineering J. Am. Chem. Soc. 2012, 134 (49), 20103–20109