Ionic Combisomes: A New Class of Biomimetic Vesicles to Fuse with Life

Abstract

The construction of biomembranes that faithfully capture the properties and dynamic functions of cell membranes remains a challenge in the development of synthetic cells and their application. Here a new concept for synthetic cell membranes based on the self‐assembly of amphiphilic comb polymers into vesicles, termed ionic combisomes (i‐combisomes) is introduced. These combs consist of a polyzwitterionic backbone to which hydrophobic tails are linked by electrostatic interactions. Using a range of microscopies and molecular simulations, the self‐assembly of a library of combs in water is screened. It is discovered that the hydrophobic tails form the membrane's core and force the backbone into a rod conformation with nematic‐like ordering confined to the interface with water. This particular organization resulted in membranes that combine the stability of classic polymersomes with the biomimetic thickness, flexibility, and lateral mobility of liposomes. Such unparalleled matching of biophysical properties and the ability to locally reconfigure the molecular topology of its constituents enable the harboring of functional components of natural membranes and fusion with living bacteria to “hijack” their periphery. This provides an almost inexhaustible palette to design the chemical and biological makeup of the i‐combisomes membrane resulting in a powerful platform for fundamental studies and technological applications.

Trendbericht: Makromolekulare Chemie 2023

“…51) Ganz andere Zell-Material-Interaktionen zeigte das Material von Rodriguez-Emmenegger und Team: ionische Combisome, die sowohl mit Liposomen als auch mit lebenden Bakterien fusionieren. 52) Die relative Häufigkeit von Beiträgen aus der makromolekularen Chemie in der Biomedizin zeigt, wie bedeutend und beliebt dieses Forschungsfeld ist. Vom weichen Hydrogel über biomimetische Strukturen bis hin zu zähen Implantaten sind viele Eigenschaftsbereiche von Makromolekülen ver-treten.…”

Hydrophobin Bilayer as Water Impermeable Protein Membrane

“…14−17 Artificial membranes with controlled permeability have been formed using several other building blocks besides lipids, 18 such as fatty acids, synthetic lipids, (block co)polymers, 19−21 engineered proteins, or peptides. 22,23 Other possible building blocks for artificial membranes are amphiphilic proteins like the protein HFBI, which has been used to form pure protein membranes. 24 HFBI is a globular protein from the family of class II hydrophobins produced by the filamentous fungus Trichoderma reesei.…”

“…The regulation of water permeability is particularly important for maintaining cell homeostasis, enabling the cell to respond to external influences, such as salt concentration or pH. Controlling water permeability is also relevant in the field of biomimetics for potential biotechnological and biomedical applications, − for instance as nanocarriers, and has therefore been addressed by various experimental and theoretical studies. − The lipid composition, as well as the content of proteins, channels, or nanoparticles, strongly influences the permeability, as has been shown in numerous experimental studies using planar lipid bilayers − or liposomes. − Artificial membranes with controlled permeability have been formed using several other building blocks besides lipids, such as fatty acids, synthetic lipids, (block co)­polymers, − engineered proteins, or peptides. , Other possible building blocks for artificial membranes are amphiphilic proteins like the protein HFBI, which has been used to form pure protein membranes …”

Synthetic Evolution of a Supramolecular Harpooning Mechanism to Immobilize Vesicles at Antifouling Interfaces

“…This approach has been expanded to generate new amphiphiles that can be used either to develop injectable hydrogels containing vesicles for immunotherapy and regenerative medicine, [ 29 ] or polymer nanoparticle hydrogel‐based vaccines, [ 33 ] as well as a means to generate a new family of vesicles termed i‐combisomes that can fuse with living bacteria. [ 18 ]…”