Dendrimersome Synthetic Cells Harbor Cell Division Machinery of Bacteria

Abstract

as compartmentalization, transport of molecules, metabolism, growth, and ideally, replication through cell division. The latter is one of the hallmarks of life and one of the most intriguing phenomena exhibited by living organisms. [1] Beyond that, synthetic cells could comprise features that biological ones lack, such as an increased stability against environmental conditions, or much simplified programmability for desired new functions to be utilized in (bio)technological applications. [2] One obvious strategy for designing such hybrid protocells includes encapsulating components of the active cell machinery into artificial cell-like compartments. The most prominent methods involve the use of liposomes, which are lipid bilayer compartments that mimic cells with respect to their size and provide basic biochemical functionalities. [3] In these systems, reconstitution of minimal components of cell division has been demonstrated. [3b] A notable example is the MinCDE protein system, which is the spatial regulator of cell division for manyThe integration of active cell machinery with synthetic building blocks is the bridge toward developing synthetic cells with biological functions and beyond. Self-replication is one of the most important tasks of living systems, and various complex machineries exist to execute it. In Escherichia coli, a contractile division ring is positioned to mid-cell by concentration oscillations of self-organizing proteins (MinCDE), where it severs membrane and cell wall. So far, the reconstitution of any cell division machinery has exclusively been tied to liposomes. Here, the reconstitution of a rudimentary bacterial divisome in fully synthetic bicomponent dendrimersomes is shown. By tuning the membrane composition, the interaction of biological machinery with synthetic membranes can be tailored to reproduce its dynamic behavior. This constitutes an important breakthrough in the assembly of synthetic cells with biological elements, as tuning of membrane-divisome interactions is the key to engineering emergent biological behavior from the bottom-up.

Protein‐Based Patterning to Spatially Functionalize Biomimetic Membranes

“…It should be noted that we fabricated our two model carrier systems coated with lipid bilayers. Indeed, negatively charged membranes, lipid or polymer-based, [39] act as enabling platforms for our protein-based patterning tool. Therefore, by generating lipid vesicles and coating 3D-printed microstructures with SLBs, we incorporate a multi-purpose layer to which diverse functional ligands can be anchored, resulting in the endowment of the coated structures with well-defined properties for interacting or sensing the environment around them.…”

Zwitterionic Dendrimersomes: A Closer Xenobiotic Mimic of Cell Membranes

“…The overall, higher thermal and chemical stability are well in line with the higher mechanical stability as determined by puncture AFM. [30] The higher stability of z-DSs compared to liposomes is likely related to additional cohesive interactions stemming either from the hydrophobic dendrons or the highly hydrated zwitterionic PC. To elucidate the contributors to the enhanced stability of z-DSs we compared its resistance to high temperature with other classic dendrimersomes.…”

Glycan-Driven Formation of Raft-Like Domains with Hierarchical Periodic Nanoarrays on Dendrimersome Synthetic Cells

“…64−68 JDs consist of hydrophilic and hydrophobic dendrons linked to opposite sides of a core unit, offering precise control over membrane properties such as flexibility, lateral mobility, thickness, and stability, mimicking cell membranes effectively. 61,63,69,70 We utilized Janus glycodendrimers (JGDs), wherein linear or branched oligosaccharides were diluted in a defined way among tri(ethylene oxide) (3EO) units in the hydrophilic dendrons within one molecule to investigate glycan−lectin interactions. 58−60,71−77 We discovered that the assembly of these sequence-defined JGDs resulted in cell-membrane mimics featuring nanoarrays of glycan moieties organized in lamellar or hexagonal patterns with significantly enhanced glycan reactivity compared to that observed in GDSs where glycans densely packed and resulted in flat and uniform membranes without nanoarrays.…”

“…In our previous work, we demonstrated the formation of bilayer membranes featuring modulated phases, including lamellar and hexagonal nanoarrays, by segregation of glycan moieties within the hydrophilic fragment of the amphiphiles. − To achieve these nanoarrays, we employed new synthetic alternatives to natural lipids known as amphiphilic Janus dendrimers (JDs). − Broad libraries of JDs have been synthesized to study the biological mechanism involved in cellular recognition, drug and gene delivery, and nanomedicine. − JDs consist of hydrophilic and hydrophobic dendrons linked to opposite sides of a core unit, offering precise control over membrane properties such as flexibility, lateral mobility, thickness, and stability, mimicking cell membranes effectively. ,,, We utilized Janus glycodendrimers (JGDs), wherein linear or branched oligosaccharides were diluted in a defined way among tri­(ethylene oxide) (3EO) units in the hydrophilic dendrons within one molecule to investigate glycan–lectin interactions. − ,− We discovered that the assembly of these sequence-defined JGDs resulted in cell-membrane mimics featuring nanoarrays of glycan moieties organized in lamellar or hexagonal patterns with significantly enhanced glycan reactivity compared to that observed in GDSs where glycans densely packed and resulted in flat and uniform membranes without nanoarrays. , The nanoarray formation in monocomponent membranes was programmed by the composition of hydrophilic moieties, i.e., the ratio of glycan:3EO. Nevertheless, this discovery prompted us to explore the potential for achieving and tuning glycan nanoarrays within multicomponent GDS membranes.…”