Amphiphiles, molecules that contain both hydrophilic and hydrophilic parts, can assemble in water into either spherical or cylindrical micelles or membranes depending on the molecular composition and size. Membranes are a critical component of biological organisation, and natural amphiphiles (phospholipids) set the limits within and between cells. Membranes have to avoid contact between their edges and water, and this drives their deformation to form enclosed structures are known as vesicles typically spherical to minimise surface area. We have been particularly interested in polymeric amphiphiles comprising hydrophilic and hydrophobic blocks joined together. The macromolecular nature of the copolymers imposes two unique features to amphiphilic copolymer membranes: (i) hydrophobic entanglement (Battaglia et al JACS 2005) and (ii) hydrophilic brush-like configuration (Smart et al Soft Matter 2009).
These features make block copolymer vesicles (aka 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 polymersome with a dense hydrophilic layer that controls both colloidal stability and interaction with its environment. We have been studying polymersomes formation kinetic for several years and learned how to control both bottom-up or top-down approaches to engineering the polymersome shape topology, making both spherical, tubular and more complex high-genus structures. We have also developed a way to control the polymersome surface topology by combining different polymersome-forming copolymers and, in doing so, tuning the interaction between them.
We have been studying the formation mechanism of polymersomes for several years and these can be divided into two approaches: from bulk polymers (top-down route) or from unimers, meaning single block copolymer chains (bottom-up route).
Block copolymers have the tendency to assemble in the solid-state, creating complex mesoscopic structures whose architecture is controlled by the blocks interactions and molar ratios. The transition from such a state to a single vesicle requires both the solvent (i.e. the water) and the single blocks to diffuse one another. However, amphiphilic copolymers, like all amphiphiles, are lyotropic meaning that their mesoscopic organisation changes as a function of the copolymer/water ratio. We mapped out the phase diagrams of vesicles forming copolymers (Battaglia et al Nature Mater 2005 and Battaglia et al Macromolecules 2006).
Polymersomes formation is strictly controlled by the phase transitions and how copolymers rearrange. We observed that the kinetics of formation begin following a sub-diffusional regime where lyotropic phases rearrange to form lamellar structures that shed into vesicles (Battaglia et al J. Phys Chem B 2006).
This means that if we control the original block copolymer film we can control the final size and destruction of the vesicle (Howse et al Nature Mater 2009). Also, such properties combined with the intrinsic low diffusivity of polymers allow the emergence of metastable phases including, lamellarsomes (Battaglia et al Soft Matter 2006), myelin-like structures (Battaglia et al. Angew. Chem. Int. Ed. 2006) and tubular polymersomes (Robertson et al ACS Nano 2014)
We can dissolve the polymersomes forming block copolymers unimolecularly and change one block solvency to trigger self-assembly. We can achieve this, either by starting with a non-selective solvent and change it gradually for a selective one or using copolymers having one of the blocks with polarity sensitive to pH, temperature or any other controllable variable. Alternatively, we can trigger self-assembly by polymerising from another soluble polymer an insoluble block using the so-called polymerization induced self-assembly (PISA). In all these cases, the polymersome emerges from the collective assembly of the different unimers. We identified two different mechanisms:
(i) the copolymer hydrophobic/hydrophilic ratio or packing factor is changed gradually allowing the formation and evolution of spherical, cylindrical micelles and finally vesicles (Fernyhough et al Soft Matter 2009 and Blanazs et al JACS 2011).
(ii) The copolymer packing factor is changed abruptly and the first nucleation leads to the formation of disk-like micelles which enclose into vesicles. If the unimer pool is maintained, the vesicle continues growing asymmetrically giving rise to high genus vesicles such as toroidal vesicles, double toroid and so on (Pearson et al Macromolecules 2013 Contini et al iScience 2018
"Topology" derives from the Greek τοποσ, 'topos' (space) and 'logos' (discourse) is the study of geometrical properties and spatial relations unaffected by continuous shape changes. We use here the term surface topology to define the formation of patterns on the polymersomes surface which arise as a consequence of membrane-confined interactions. If we forced two different membrane-forming copolymers to self-assemble into the same vesicle, the interaction between the two (often repulsive) will lead to the formation of different domains (LoPresti et al ACS Nano 2011). As shown below, we can use such interactions to control patterning (Ruiz-Perez et al Science Adv. 2016, the polymersome topography (LoPresti et al ACS Nano 2011) and symmetry (Joseph et al Science Adv. 2017)