Molecular recognition and organizational and polyvalent effects in vesicles induce the formation of artificial multicompartment cells as model systems of eukaryotes.

Abstract

Researchers have become increasingly interested in the preparation and characterization of artificial cells based on amphiphilic molecules. In particular, artificial cells with multiple compartments are primitive mimics of the structure of eukaryotic cells. Endosymbiotic theory, widely accepted among biologists, states that eukaryotic cells arose from the assembly of prokaryotic cells inside other cells. Therefore, replicating this process in a synthetic system could allow researchers to model molecular and supramolecular processes that occur in living cells, shed light on mass and energy transport through cell membranes, and provide a unique, isolated space for conducting chemical reactions. In addition, such structures can serve as drug delivery systems that encapsulate both bioactive and nonbiocompatible compounds. In this Account, we present various coating, incubation, and electrofusion strategies for forming multicompartment vesicle systems, and we are focusing on strategies that rely on involving molecular recognition of complementary vesicles. All these methods afforded multicompartment systems with similar structures, and these nanoparticles have potential applications as drug delivery systems or nanoreactors for conducting diverse reactions. The complementarity of interacting vesicles allows these artificial cells to form, and the organization and polyvalency of these interacting vesicles further promote their formation. The incorporation of cholesterol in the bilayer membrane and the introduction of PEG chains at the surface of the interacting vesicles also support the structure of these multicompartment systems. PEG chains appear to destabilize the bilayers, which facilitates the fusion and transport of the small vesicles to the larger ones. Potential applications of these well-structured and reproducibly produced multicompartment systems include drug delivery, where researchers could load a cocktail of drugs within the encapsulated vesicles, a process that could enhance the bioavailability of these substances. In addition, the production of artificial cells with multiple compartments provides a platform where researchers could carry out individual reactions in small, isolated spaces. Such a reactive space can avoid problems that occur when the environment can be destructive to reactants or products or when a diverse set of compounds difficult to obtain in a conventional reactor space are produced. Our work on these artificial cells with multicompartment structures also led us to formulate a hypothesis on the processes that possibly generated eukaryotic cells. We hope both that our research efforts will excite interest in these nanoparticles and that this research could lead to systems designed for specific scientific and technological applications and further insights into the evolution of eukaryotic cells.