Thermally Induced Reversible Self‐Assembly of Apoferritin–Block Copolymer Complexes

Abstract

higher mammals. [15] Ferritins are spherical iron storage containers, most of which consists of 24 subunits, with an outer diameter of 12 nm and an inner cavity of 8 nm. [16] Their ability to nucleate and store inorganic materials has led to their usage as scaffolds for 2D [17] and 3D [18] oriented inorganic nanostructures. Ferritin cage can also be further modified to enable the design of stimuli-responsive assemblies. Polymers can impart the systems with properties untypical for highly ordered structures, like self-healing [19] and thermo-responsiveness. Covalently modified thermo-responsive ferritin has been reported, [20] but the modification requires extra synthesis steps and is irreversible. Electrostatic self-assembly is an appealing choice to design environmentally responsive systems, as it is straightforward to employ and can be reversed by increasing the electrolyte concentration, which screens the Coulombic interactions between the components. [21] Examples of such systems include, for example, protein cage directed binary nanoparticle superlattices. [22] Here, we present an attempt to produce multi-responsive materials by complexing apoferritin (ferritin with no cargo in the inner cavity, aFT) with synthetic block copolymers consisting of cationized poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) and thermo-responsive poly[di(ethylene glycol) methyl ether methacrylate] (PDEGMA) (Figure 1). The system is sensitive to both temperature and concentration of small electrolytes in the solution. PDEGMA displays lower critical solution temperature (LCST) type behavior, meaning it is hydrophilic at low temperatures, but turns hydrophobic with increasing temperature. The used polymers were linear diblock or triblock chains (sequence: PDMAEMA-PDEGMA-PDMAEMA).All polymers were synthesized using atom transfer radical polymerization (ATRP) reactions, which is a well-studied method for producing linear polymers with low dispersity. [23] The blocks were polymerized by synthesizing first a homopoly mer, which was purified and used as a macro initiator for the diblock copolymer. The triblock copolymer was similarly initiated from purified diblock copolymer. The length of the blocks and their ratio to one another is crucial for obtaining both electrostatically self-assembling and multi-responsive system. The cationic block must be long enough to have sufficient charge density for strong binding between the polymer and aFT, but not too long to cause aggregation regardless of the state of the thermoresponsive block. The LCST point of the polymer depends on the length of the PDEGMA block, which also needs to be long enough to induce sufficient hydrophobicity to aFT to induce Thermo-Responsive Self-Assembly Protein cages are interesting building blocks for functional supramolecular assemblies. A multi-responsive system composed of apoferritin and thermoresponsive block copolymers complexed through electrostatic interactions is described here. The polymers are linear chains with cationic and thermoresponsive blocks, and ...

A Modeling-Based Design to Engineering Protein Hydrogels with Random Copolymers

“…A multiresponsive complex composed of apoferritin and block copolymers which dynamically self-assemble by altering the temperature and electrolyte concentration of the solutions was developed. 21 Within the prospect of direct enzyme−polymer noncovalent complexation, amphiphilic heteropolymers offer a versatile approach for protein solubilization and stabilization. The capability to synthesize random heteropolymers with reliable control over the statistical monomer distribution affords promising developments toward a rational match between the surface patterns of natural proteins and polymer side chains.…”

“…Moreover, the expansion–contraction cycles and therefore the self-healing properties were tested on the hydrogel-based crystal by alternating the divalent and monovalent metal-salt solution. A multiresponsive complex composed of apoferritin and block copolymers which dynamically self-assemble by altering the temperature and electrolyte concentration of the solutions was developed …”