Peptide-Based Coacervate Protocells with Cytoprotective Metal–Phenolic Network Membranes

Abstract

Protocells have garnered considerable attention from cell biologists, materials scientists, and synthetic biologists. Phaseseparating coacervate microdroplets have emerged as a promising cytomimetic model because they can internalize and concentrate components from dilute surrounding environments. However, the membrane-free nature of such coacervates leads to coalescence into a bulk phase, a phenomenon that is not representative of the cells they are designed to mimic. Herein, we develop a membranized peptide coacervate (PC) with oppositely charged oligopeptides as the molecularly crowded cytosol and a metal−phenolic network (MPN) coating as the membrane. The hybrid protocell efficiently internalizes various bioactive macromolecules (e.g., bovine serum albumin and immunoglobulin G) (>90%) while also resisting radicals due to the semipermeable cytoprotective membrane. Notably, the resultant PC@MPNs are capable of anabolic cascade reactions and remain in discrete protocellular populations without coalescence. Finally, we demonstrate that the MPN protocell membrane can be postfunctionalized with various functional molecules (e.g., folic acid and fluorescence dye) to more closely resemble actual cells with complex membranes, such as recognition molecules, which allows for drug delivery. This membrane-bound cytosolic protocell structure paves the way for innovative synthetic cells with structural and functional complexity.

Multifunctional Metal–Phenolic Composites Promote Efficient Periodontitis Treatment via Antibacterial and Osteogenic Properties

“…Au@MPN was prepared using a one-pot method according to our previous description . Specifically, 20 μL of 50 nm AuNPs, 20 μL of 10 mg mL –1 TA, and 20 μL of 2 mg mL –1 SrCl 2 were added into 400 μL of H 2 O.…”

“…Metal–phenolic networks (MPNs) are amorphous metal–organic frameworks (MOFs) formed by polyphenols and metal ions, which are synthesized in mild conditions with simple steps, , avoiding toxic precursors and solvents as well as harsh conditions . The rapid coordination kinetics and unique adhesive nature of MPNs allow it to function as a coating .…”

Self-assembly of stabilized droplets from liquid–liquid phase separation for higher-order structures and functions

“…However, the stability of these membranes is highly sensitive to environmental changes such as ionic strength, which could pose challenges in maintaining the desired state of the droplets. Given that the lipid membranes are sensitive to environmental changes, metal-organic systems with enhanced stability have been used to membranize coacervate droplets 38 . Polyphenols coordinate with metal ions can form the metal–phenolic networks (MPNs) that can fast self-assemble from various building blocks on the surface of the coacervates and provide the protocells with physical and chemical stability, surface modifiability and high biocompatibility.…”

Colorimetric sensing for translational applications: from colorants to mechanisms

“…This requires the rationale design of coating ligand/substrate for good nanoscale recognitions on scaffolds ( e.g. , NP, 341,353 antibody, 354 polymer, 355,356 biocondensate 357–359 ), including optimized accessibility, homogeneity, orientation, and functionality. For example, Ulijn et al demonstrated that enzymatic unveiling of surface-bound zwitterionic tetrapeptides through MMP-9 can activate the self-assembly of AuNPs.…”