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Giant lipid vesicles have been used extensively as a synthetic cell model to recapitulate various life-like processes, including in vitro protein synthesis, DNA replication, and cytoskeleton organization. Cell-sized lipid vesicles are mechanically fragile in nature and prone to rupture due to osmotic stress, which limits their usability. Recently, peptide vesicles have been introduced as an alternative chassis material for synthetic cells that are more robust and stable than lipid vesicles, and can withstand harsh conditions including pH, thermal, and osmotic variations. In this work, we combine coarse-grained molecular simulation, enhanced sampling free energy calculations, Gaussian process regression, and Bayesian optimization to construct an active learning screening for diblock amphiphilic elastin-like polypeptides capable of forming thermodynamically stable vesicular structures suitable for the self-assembly of synthetic peptide vesicles. Our computational screen identifies a number of promising sequences that form peptidic vesicles with high thermodynamic stabilities relative to isolated peptides in bulk solvent on the order of 10-15 k B T per amino acid residue. 

In the pursuit of understanding life, model membranes made of phospholipids were envisaged decades ago as a platform for the bottom-up study of biological processes. Micron-sized lipid vesicles have gained great acceptance as their bilayer membrane resembles the natural cell membrane. Important biological events involving membranes, such as membrane protein insertion, membrane fusion, and intercellular communication, will be highlighted in this review with recent research updates. We will first review different lipid bilayer platforms used for incorporation of integral membrane proteins and challenges associated with their functional reconstitution. We next discuss different methods for reconstitution of membrane fusion and compare their fusion efficiency. Lastly, we will highlight the importance and challenges of intercellular communication between synthetic cells and synthetic cells-to-natural cells. We will summarize the review by highlighting the challenges and opportunities associated with studying membrane–membrane interactions and possible future research directions. 

We demonstrate the facile and robust generation of giant peptide vesicles by using an emulsion transfer method. These robust vesicles can sustain chemical and physical stresses. The peptide vesicles can host cell-free expression reactions by encapsulating essential ingredients. We show the incorporation of another cell-free expressed elastin-like polypeptide into the existing membrane of the peptide vesicles. 

Giant lipid vesicles have been used extensively as a synthetic cell model to recapitulate various life-like processes, including in vitro protein synthesis, DNA replication, and cytoskeleton organization. Cell-sized lipid vesicles are mechanically fragile in nature and prone to rupture due to osmotic stress, which limits their usability. Recently, peptide vesicles have been introduced as a synthetic cell model that would potentially overcome the aforementioned limitations. Peptide vesicles are robust, reasonably more stable than lipid vesicles and can withstand harsh conditions including pH, thermal, and osmotic variations. This mini-review summarizes the current state-of-the-art in the design, engineering, and realization of peptide-based chassis materials, including both experimental and computational work. We present an outlook for simulation-aided and data-driven design and experimental realization of engineered and multifunctional synthetic cells.