Application of polymersomes in membrane protein study and drug discovery: Progress, strategies, and perspectives

Abstract

Membrane proteins (MPs) play key roles in cellular signaling pathways and are responsible for intercellular and intracellular interactions. Dysfunctional MPs are directly related to the pathogenesis of various diseases, and they have been exploited as one of the most sought‐after targets in the pharmaceutical industry. However, working with MPs is difficult given that their amphiphilic nature requires protection from biological membrane or membrane mimetics. Polymersomes are bilayered nano‐vesicles made of self‐assembled block copolymers that have been widely used as cell membrane mimetics for MP reconstitution and in engineering of artificial cells. This review highlights the prevailing trend in the application of polymersomes in MP study and drug discovery. We begin with a review on the techniques for synthesis and characterization of polymersomes as well as methods of MP insertion to form proteopolymersomes. Next, we review the structural and functional analysis of the different types of MPs reconstituted in polymersomes, including membrane transport proteins, MP complexes, and membrane receptors. We then summarize the factors affecting reconstitution efficiency and the quality of reconstituted MPs for structural and functional studies. Additionally, we discuss the potential in using proteopolymersomes as platforms for high‐throughput screening (HTS) in drug discovery to identify modulators of MPs. We conclude by providing future perspectives and recommendations on advancing the study of MPs and drug development using proteopolymersomes.

Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery

“…Although synthetic molecules that trigger dynamic membrane deformation and fusion have been reported, − a molecular approach that enables endocytosis-like transport in which membrane deformation is synchronized with substance transport remains critically unexplored. Artificial vesicles such as polymersomes and dendrimersomes have also been developed for the design of dynamic membrane materials. − However, adsorptions of colloidal objects onto membranes or changes in the external environment such as osmotic pressure are required in these systems for changing the membrane curvature or membrane tension, respectively, to induce membrane deformations. An important consideration for the realization of endocytosis-like fission is how to bias vesicles toward outside-in fission rather than inside-out fission.…”

A Practical Guide to Preparation and Applications of Giant Unilamellar Vesicles Formed via Centrifugation of Water-in-Oil Emulsion Droplets

“…In addition, during the construction of artificial cells [3], which are cell mimicries in terms of the functions of molecular aggregates, the multiple nested structures of GMVs are likely to cause defects while sensing external stimuli and controlling membrane dynamics to release encapsulated materials. Therefore, GUVs have drawn attention to the construction of artificial cells and model cell membranes [4][5][6][7][8][9][10][11].…”

“…When GUVs are composed of biocompatible materials, they can be implanted in vivo. Liposomes as well as polymersomes play an important role in the functionalization of membrane proteins [10]. Therefore, GUV-based artificial cells have recently attracted attention as a new tool for pharmaceutical and medical applications.…”

Advances in Biohybridized Planar Polymer Membranes and Membrane‐Like Matrices

“…Accordingly, a number of membrane proteins were successfully integrated mostly into the membranes of polymer vesicles known as polymersomes. [10] Among the most prominent examples are transmembrane channel proteins such as E. coli outer membrane proteins, [11,12] staphylococcal α-haemolysin [13,14] and aquaporins, [15 -18] which we will discuss below in the context of planar supported polymer membranes, and Mycobacterium smegmatis porin A (MspA) [19] with its published record in DNA sequencing. [20] Integral membrane receptor proteins, e. g. ferric hydroxamate uptake protein component A (FhuA), [21] and protein complexes (photosynthesis complex I, II; [22] ) have also been incorporated into polymer membranes.…”