# Nanomechanical imaging of protein dynamics via programmable DNA interactions

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2021 · $319,970

## Abstract

PROJECT SUMMARY
The proposed research will address challenges in imaging dynamic structures of proteins and protein
complexes in solution. Fluorescence microscopy is currently the dominant technique for chemically specific
imaging in solution. Although super-resolution techniques have dramatically pushed the resolution limits of
fluorescence microscopy, it is still a major challenge to obtain images of single-molecules and molecular
complexes with resolutions comparable to electron microscopy and X-ray crystallography. Our proposed
research will develop an atomic force microscopy (AFM) platform that harnesses short-lived DNA/DNA
interactions to achieve imaging and three-dimensional reconstruction of chemical groups within individual
proteins, multi-enzyme complexes, and complexes between proteins, RNA and DNA with near atomic
resolution and in physiologically relevant conditions. Enhancing the imaging speed will enable observation of
structural transitions. These capabilities are enabled by a series of innovations: (1) the use of short fragments
of DNA as imaging labels, wherein the sequence of DNA encodes color information, (2) the use of short-lived,
far from equilibrium interactions that boost resolution and chemical specificity, and (3) the use of specially
designed T-shaped atomic force microscopy cantilevers that allow detecting short-lived interactions. The
resulting microscopy platform will have a broad impact across many biomedical fields by providing structural
information about proteins and protein complexes that are difficult to study via the current methods.

## Key facts

- **NIH application ID:** 10217200
- **Project number:** 5R01GM130948-03
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Ozgur Sahin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $319,970
- **Award type:** 5
- **Project period:** 2019-09-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217200

## Citation

> US National Institutes of Health, RePORTER application 10217200, Nanomechanical imaging of protein dynamics via programmable DNA interactions (5R01GM130948-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10217200. Licensed CC0.

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