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# Expanding the DNA Nanotechnology Toolbox: Hierarchical Assembly and Self-Sorting of DNA Tiles With Precisely Controlled Hydrophobic Behavior

## Details

**Authors** Yihao Wu, Muhammad Ghufran Rafique, Christopher Saab, Hanadi Sleiman

**Year** 2026

**Publisher** Angewandte Chemie International Edition

**Kind of work** article

**Discipline** Chemistry

**Secondary disciplines** Materials Science

[Read it at the publisher](https://doi.org/10.1002/anie.1147906) 
10.1002/anie.1147906

## In authors' words

### Abstract

DNA self-assembly expands through non-natural nucleotides with tunable hydrophobic effects in double-crossover tiles. Sequence-defined amphiphiles regulate hierarchical assembly order, enabling quantized star architectures and spherical nucleic acids. Narcissistic self-sorting allows distinct populations from identical sequences, demonstrating extensibility to other DNA nanostructures and enabling protein-like assembly pathways.

### What they set out to do (purpose)

To expand DNA nanotechnology by using non-natural, hydrophobicity-tunable nucleotides in DNA tiles to control the order and outcome of hierarchical self-assembly.

### Who or what was studied (sample)

Synthetic double-crossover DNA tiles modified with sequence-defined hydrophobic (amphiphilic) non-natural nucleotides.

### How they did it (methods)

DNA tiles bearing systematically varied hydrophobic modifications were self-assembled in vitro; resulting architectures (quantized stars vs. crosslinked spherical nucleic acids) and self-sorting behavior were characterized as a function of hydrophobic strength.

### What they found (results)

Tuning the hydrophobic strength of modified DNA tiles sets a threshold that determines assembly order — weak hydrophobicity yields base-pairing-first, quantized star architectures, while strong hydrophobicity yields hydrophobic-collapse-first, crosslinked spherical nucleic acids — and also enables 'narcissistic' self-sorting of distinct populations from identical sequences.

## Commentary

### In short

A hydrophobicity threshold is a Distinction (D) that switches which part-whole assembly pathway is taken, so the same DNA tile components combine into different hierarchical wholes (a Systems, S, structure) depending on which side of that threshold they fall on.

**Patterns it shows** D, S

**Added** 2026-09-16

**How to cite this** Yihao Wu, Muhammad Ghufran Rafique, Christopher Saab, Hanadi Sleiman (2026). Expanding the DNA Nanotechnology Toolbox: Hierarchical Assembly and Self-Sorting of DNA Tiles With Precisely Controlled Hydrophobic Behavior. Angewandte Chemie International Edition.