Stimuli-responsive polypeptide vesicles by conformation-specific assembly

Abstract

In biology, lipids are well known for their ability to assemble into spherical vesicles. Proteins, in particular virus capsids, can also form regular vesicle-like structures, where the precise folding and stable conformations of many identical subunits directs their self-assembly. Functionality present on these subunits also controls their disassembly within the cellular environment, for example, in response to a pH change. Here, we report the preparation of diblock copolypeptides that self-assemble into spherical vesicular assemblies whose size and structure are dictated primarily by the ordered conformations of the polymer segments, in a manner similar to viral capsid assembly. Furthermore, functionality was incorporated into these molecules to render them susceptible to environmental stimuli, which is desirable for drug-delivery applications. The control of assembly and function exhibited in these systems is a significant advance towards the synthesis of materials that can mimic the precise three-dimensional assembly found in proteins.

Self‐assembly and responsiveness of polypeptide‐based block copolymers: How “Smart” behavior and topological complexity yield unique assembly in aqueous media

“…81,86 Other reports in literature have shown vesicle formation for copolypeptide amphiphiles that contain two blocks of naturally occurring amino acids; one block being a rod-like, hydrophobic helix and the other a polyelectrolyte serving to stabilize the assembly through electrostatic interaction with water. 75,[78][79][80]82,87 Deming and coworkers have performed seminal work in this area, and the physical behavior of these vesicle-forming copolypeptides is well illustrated through their work. For example, they studied the aggregation behavior of PLys-b-poly(L-leucine) (PLys-b-PLLeu) copolymers; the PLeu was employed as due to its hydrophobicity and its ability to form stable helices.…”

Bursting of sensitive polymersomes induced by curling

“…Moreover, targeted transport can be achieved by taking advantage of the many possibilities to endfunctionalize the copolymers (5). The controlled release of therapeutic substances can also be integrated through the use of copolymers with blocks that respond to chemical stimuli such as hydrolysis (6,7), oxidation (8) or reduction (9) reaction, and pH changes (10)(11)(12)(13)(14)(15)(16)(17). Common strategies have been to use hydrophobic blocks that can progressively degrade or convert into hydrophilic moieties or to use a cleaveable linkage between hydrophobic and hydrophilic blocks.…”

Interfacial assembly of protein–polymer nano-conjugates into stimulus-responsive biomimetic protocells

“…Artificial cell-like architectures have been developed based on phospholipid vesicles [10][11][12][13][14][15] , polymersomes 16,17 , polymeric [18][19][20] or polypeptide capsules 21,22 , organic [23][24][25][26] and inorganic colloidosomes 27,28 , dendrimersomes 29 multi-compartment vesicles [30][31][32] and membrane-free peptide (polymer)/nucleotide micro-droplets (coacervates) [33][34][35] . In contrast, there are few reports on the use of protein-based building blocks as structural and functional modules for the spontaneous self-assembly of biomimetic protocells even though the intrinsic biocompatibility, biodegradability and biofunctionality of protein membranes offer important advantages.…”