Multicompartment Polymer Vesicles with Artificial Organelles for Signal‐Triggered Cascade Reactions Including Cytoskeleton Formation

Abstract

Organelles, i.e., internal subcompartments of cells, are fundamental to spatially separate cellular processes, while controlled intercompartment communication is essential for signal transduction. Furthermore, dynamic remodeling of the cytoskeleton provides the mechanical basis for cell shape transformations and mobility. In a quest to develop cell‐like smart synthetic materials, exhibiting functional flexibility, a self‐assembled vesicular multicompartment system, comprised of a polymeric membrane (giant unilamellar vesicle, GUV) enveloping polymeric artificial organelles (vesicles, nanoparticles), is herein presented. Such multicompartment assemblies respond to an external stimulus that is transduced through a precise sequence. Stimuli‐triggered communication between two types of internal artificial organelles induces and localizes an enzymatic reaction and allows ion‐channel mediated release from storage vacuoles. Moreover, cytoskeleton formation in the GUVs' lumen can be triggered by addition of ionophores and ions. An additional level of control is achieved by signal‐triggered ionophore translocation from organelles to the outer membrane, triggering cytoskeleton formation. This system is further used to study the diffusion of various cytoskeletal drugs across the synthetic outer membrane, demonstrating potential applicability, e.g., anticancer drug screening. Such multicompartment assemblies represent a robust system harboring many different functionalities and are a considerable leap in the application of cell logics to reactive and smart synthetic materials.

Combinatorial Strategy for Studying Biochemical Pathways in Double Emulsion Templated Cell‐Sized Compartments

“…This is in contrast to polymer GUVs formed by direct self‐assembly in dilute solutions, which had a larger size distribution, in the range between 2 to 40 m. [ 28,59 ]…”

“…This is in contrast to polymer GUVs formed by direct self-assembly in dilute solutions, which had a larger size distribution, in the range between 2 to 40 µm. [28,59] Additionally, as the amphiphilic diblock copolymer PDMS 26 -b-PMOXA 9 was employed for assembly of the compartments, we expect the GUVs to be impermeable to small molecules. [24,28] Nonetheless, since the method of GUV formation influences the mode of self-assembly, it might also induce changes in the membrane permeability.…”

Cell mimicry as a bottom‐up strategy for hierarchical engineering ofnature‐inspiredentities

“…Compartmentalization can also be driven by liquid–liquid phase separation (LLPS) to create nonmembrane bound organelles, as reviewed elsewhere (Crowe & Keating, 2018; Ma et al, 2020). LLPS serves as a means to mimic organization of cellular fluids, as seen in, for example, nucleoli and cytoplasmic structures (Crowe & Keating, 2018), and the condensates address the crowded intracellular environment of cells (Belluati et al, 2020). Polymer stabilized coacervates were used to mimic the cytosolic crowding (Yewdall et al, 2019) and coacervate systems were encapsulated into liposomes, which allowed for spatial organization of transcription.…”

Construction of Eukaryotic Cell Biomimetics: Hierarchical Polymersomes‐in‐Proteinosome Multicompartment with Enzymatic Reactions Modulated Protein Transportation

“…Multi‐compartmentalized microstructured assemblies have demonstrated their potential application in the field of drug delivery, drug screening, microreactors, biomaterials, etc. [ 13,23,24 ] They might be used for advancing cellular model design to delineate some complex multistep processes of modern living cell. [ 13,25–27 ]…”