# Permeability selection of biologically relevant membranes matches the stereochemistry of life on Earth

**Authors:** Olivia Goode, Urszula Łapińska, Juliano Morimoto, Georgina Glover, David S. Milner, Alyson E. Santoro, Stefano Pagliara, Thomas A. Richards

PMC · DOI: 10.1371/journal.pbio.3003155 · 2025-05-20

## TL;DR

This study explores how certain membranes can select for specific sugar and amino acid stereochemistry, matching that of life on Earth.

## Contribution

The study demonstrates that hybrid membranes can uniquely select for l-amino acids and d-sugars relevant to life.

## Key findings

- Hybrid membranes select for d-ribose and d-deoxyribose sugars.
- The hybrid membrane uniquely selects for a reduced alphabet of l-amino acids, including alanine.
- Such membranes could provide stereochemical compound selection matching core metabolism of life.

## Abstract

Early in the evolution of life, a proto-metabolic network was encapsulated within a membrane compartment. The permeability characteristics of the membrane determined several key functions of this network by determining which compounds could enter the compartment and which compounds could not. One key feature of known life is the utilization of right-handed d-ribose and d-deoxyribose sugars and left-handed l-amino acid stereochemical isomers (enantiomers); however, it is not clear why life adopted this specific chirality. Generally, archaea have l-phospholipid membrane chemistries and bacteria and eukaryotes have d-phospholipid membrane chemistries. We previously demonstrated that an l-archaeal and a d-intermediate membrane mimic, bearing a mixture of bacterial and archaeal lipid characteristics (a ‘hybrid’ membrane), displayed increased permeability for several key compounds compared to bacterial-like membranes. Here, we investigate if these membranes can drive stereochemical selection on pentose sugars, hexose sugars, and amino acids. Using permeability assays of homogenous unilamellar vesicles, we demonstrate that both membranes select for d-ribose and d-deoxyribose sugars while the hybrid membrane uniquely selects for a reduced alphabet of l-amino acids. This repertoire includes alanine, the plausible first l-amino acid utilized. We conclude such compartments could provide stereochemical compound selection matching those used by the core metabolism of life.

Early in the evolution of life a biochemical network was encapsulated within a membrane compartment. This study shows that specific membrane forms can select for stereochemical compounds which match the pattern of stereochemistry used by all known living things.

## Linked entities

- **Chemicals:** d-ribose (PubChem CID 854), alanine (PubChem CID 239)
- **Species:** Archaea (taxon 2157), Bacteria (taxon 2)

## Full-text entities

- **Chemicals:** phospholipid (MESH:D010743), d-ribose (MESH:D012266), amino acids (MESH:D000596), alanine (MESH:D000409), lipid (MESH:D008055), -archaeal (-)

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12091744/full.md

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Source: https://tomesphere.com/paper/PMC12091744