Engineering Polymersome Protocells

Abstract

The field of biomimicry is embracing the construction of complex assemblies that imitate both biological structure and function. Advancements in the design of these mimetics have generated a growing vision for creating an artificial or proto- cell. Polymersomes are vesicles that can be made from synthetic, biological or hybrid polymers and can be used as a model template to build cell-like structures. In this perspective, we discuss various areas where polymersomes have been used to mimic cell functions as well as areas in which the synthetic flexibility of polymersomes would make them ideal candidates for a biomembrane mimetic. Designing a polymersome that comprehensively displays the behaviors discussed herein has the potential to lead to the development of an autonomous, responsive particle that resembles the intelligence of a biological cell.

Figure 1. A Polymersome Protocell

Polymersomes can be used as a template to create cell-like structures. Creating an autonomous particle that mimics the diverse behaviors of a cell will require incorporation of biological functionality in the membrane, the ability to trigger responses, autonomous movement, and morphological changes. Many of these functions will require organized metabolic reactions and gene expression to be housed within distinct spatial environments in the polymersome. Illustration of the mechanosensitive protein channel courtesy of David S. Goodsell and the RCSB PBD (doi:10.2210/rcsb_pdb/mom_2008_11). Dendrimer structure taken from Percec, V. and Co-authors, 2011: Self-Assembly of Janus Dendrimers into Uniform Dendrimersomes and Other Complex Architectures. Science, 328, 5981. Reprinted with permission from AAAS.

Figure 2. Polymersome membranes have been designed to interact with other polymersomes or cells and to respond to stimuli

(A, B) Modification of polymersome surfaces with antibodies and ligands can allow polymersomes to mimic some adhesive and targeting abilities of immunological cells. . (C) Composite polymersomes loaded with a porphyrin based fluorophore and dextran rupture in response to light. (D) Block copolypeptides can be induced to assemble into a membrane in response to a pH shift. (B) Adapted from reference . Reproduced by permission of The Royal Society of Chemistry. (C), (D) Adapted from references and , respectively. Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with Permission

Figure 3. The static and dynamic shape of a polymersome can be controlled through vesicle preparation methods and triggered stimulus

(a) The morphology of particles made from PS-PEO diblock copolymers can be changed to mimic the protrusions seen on dendritic cells by blending in a PS homopolymer with the copolymers during particle preparation. (b) The morphology of a peptide-decorated vesicle can be reversibly switched to that of a fiber for repeated cycles in response to a PH shift. (a) Adapted from reference . Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with Permission. (b) Adapted from reference .

Figure 4. Compartmentalization in polymer particles has been improved through the development of microfluidic techniques

(A) Double emulsions with a highly controllable number and size of internal droplets can be produced with capillary microfluidic devices. (B) By using multiple injection tubes in a microcapillary device, distinct internal compartments with controlled stoichiometry can now be encapsulated within a single particle. (a) Adapted from reference . Copyright Wiley-VCH Verlag GmbH & Co. KGaA. Reproduced with Permission. (b) Adapted from reference . Copyright American Chemical Society.

Figure 5. Approaches to increasing the complexity of polymersome bioreactors

(Top) Multiple enzymes can be positioned within a single polymersome to create a signaling cascade. (Left) An enzyme-containing polymersome can be encapsulated into an alternate environment like a cell or an organelle. (Right) A signaling cascade can be carried out between multiple polymersomes by requiring an intermediate reactant to diffuse from one vesicle to another.