# Biomimetic Construction of Abiotic Membranes Through Acylation of Cationic Diamino Acids

## TL;DR

Scientists created a new type of artificial membrane using simple chemical steps that mimic natural processes, enabling the formation of functional vesicles for synthetic biology.

## Contribution

A modular and simple method to synthesize abiotic phospholipid analogs with choline-like cations on diamino acid backbones.

## Key findings

- APAs self-assemble into vesicles under various conditions.
- The method allows tuning of headgroup charge and composition.
- APAs mimic key features of natural phospholipids.

## Abstract

Compartmentalization is a defining feature of living systems and a cornerstone of bottom‐up synthetic biology. Although phospholipids dominate modern biological membranes, their de novo synthesis in the laboratory remains chemically demanding and offers limited headgroup diversity, thereby constraining the functional scope of artificial membranes. Here, we describe a simple and modular strategy to access choline‐mimetic abiotic phospholipid analogs (APAs) that recapitulate key structural and functional features of natural phospholipids. Diamino acids serve as minimal scaffolds onto which a trimethylammonium (TMA) headgroup is introduced in a single step through carboxylate conjugation with Girard's Reagent T (GRT), generating a permanent choline‐like cation. Subsequent N‐acylation under mild aqueous conditions with prebiotically relevant thioesters yields diacylated amino GRT (DAAG) amphiphiles with a classical phospholipid topology. These APAs spontaneously self‐assemble into well‐defined vesicular structures and allow systematic tuning of headgroup charge and composition. Our approach facilitates access to chemically versatile, TMA‐functionalized membranes that expand the toolkit for constructing functional artificial membranes in synthetic biology, protocell research, and molecular delivery.

Cells produce membrane‐forming phospholipids through complex enzymatic pathways. Here, we present the in situ synthesis of a novel class of abiotic phospholipid analogs (APAs) featuring a permanent choline‐mimetic cation on diamino acid backbones. These APAs spontaneously self‐assemble into robust vesicles across a broad range of conditions.© 2026 WILEY‐VCH GmbH