# DNA nanotechnology enabled high-precision membrane engineering

> **NIH NIH R35** · YALE UNIVERSITY · 2024 · $460,625

## Abstract

PROJECT SUMMARY
Lipid-bilayer membranes form diverse and dynamic structures in cells to serve vital functions including nutrient
uptake, waste managements, signal transduction, and so on. Understanding the molecular mechanisms by
which the cell generates and changes its membrane structures has been a central task of cell biology. It is well
established that the physical and chemical properties of membranes regulate their interactions with proteins,
which in turn shape the membrane landscape. However, there are still major knowledge gaps regarding how
proteins act upon different membrane curvature and tension, especially when the membrane structure and/or
the membrane-protein interaction are transient. Cell-free systems using reconstituted membranes provide a
powerful method to study such intricate molecular interplays. However, there is still a pressing need for a
precisely engineered platform that (1) exquisitely controls the geometrical, biochemical and mechanical
properties of membranes and (2) easily allows for biochemical and structural characterization of membrane-
associating proteins. Using DNA nanotechnology, a bottom-up method that generates three-dimensional
molecular assemblies with programmable shape, stiffness, chemical modification, and motion, we propose to
build nanoengineered membranes to bridge the technical gap in membrane manipulation and to unravel the
mechanisms of protein-mediated membrane dynamics. Specifically, we will develop tools to (1) generate
accessible membranes with complex shapes for the quantitative study of curvature-dependent protein-
membrane interactions, (2) build liposomes and lipid nanodiscs with dynamically tunable tension to study the
role of membrane tension in regulating protein conformation and lipid transport, and (3) create transmembrane
nanopores with tunable size and chemical selectivity for the reconstitution of organelle-like compartments. We
expect these new tools to be enabling and potentially transformative for research in structural biology,
biophysics, mechanobiology, and synthetic biology.

## Key facts

- **NIH application ID:** 10932106
- **Project number:** 5R35GM149264-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Chenxiang Lin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $460,625
- **Award type:** 5
- **Project period:** 2023-09-20 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932106

## Citation

> US National Institutes of Health, RePORTER application 10932106, DNA nanotechnology enabled high-precision membrane engineering (5R35GM149264-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932106. Licensed CC0.

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