# UV Plasmon-Enhanced Chiroptical Spectroscopy of Membrane-Binding Proteins

> **NIH NIH R01** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2024 · $346,500

## Abstract

Summary
Circular dichroism (CD) and Raman optical activity (ROA) are chiroptical spectroscopies that provide valuable
structural information about biomolecules and pharmaceuticals under native conditions in aqueous buffer without
the need for special sample preparation or crystallization. The two methods are complementary as they probe
the circular dichroism of molecular electronic and molecular vibrational transitions, respectively. A combination
of the two methods is particularly well suited for investigating the structure of membrane binding proteins, which
remain very difficult to characterize with other biophysical characterization tools. Although in theory a combined
CD / ROA characterization has the potential for providing important structural information of membrane binding
proteins, in practice the weak sensitivities of the two spectroscopies makes it difficult to realize this potential. A
need for high sample concentrations and long acquisition times has limited a more widespread use of CD and
in particular ROA spectroscopy as tool for characterizing membrane binding proteins. This project intends to
overcome the sensitivity limitations of CD and ROA spectroscopies by developing plasmon-enhanced CD
(PECD) and surface-enhanced ROA (SEROA) spectroscopies that utilize plasmonic nanoantennas, which are
engineered nanostructures with specific electric (E) and magnetic (H) field properties as well as defined phase
properties, to enhance signal intensities. To maximize the signal enhancement, antenna substrates will be
developed with plasmon resonances in the ultraviolet (UV) so that the electromagnetic resonances can overlap
with the molecular electronic resonances of biological target molecules, facilitating strong signal intensities for
both CD and ROA. As this proposal focuses on developing PECD and SEROA as characterization tool for
membrane binding proteins, another important design component of the proposed antennas is the assembly of
a lipid membrane on the surface of the plasmonic nanoantennas to provide binding sites for membrane binding
proteins. This approach enriches the proteins of interest in electromagnetic hot spots where CD and ROA signal
enhancements are highest and allows for a spectroscopic characterization of the protein structure in its
membrane-bound form. The developed plasmon-enhanced spectroscopies will enable important new insights
into the structure and chirality of membrane-binding proteins, for instance as function of lipid compositions, and
will contribute to a greatly improved understanding of protein-membrane interactions. The specific aims of this
application are to:
Aim 1: Develop a Plasmon-Enhanced Ultraviolet CD Spectroscopy for Membrane Binding Proteins
Aim 2: Develop Plasmon Enhanced Raman Optical Activity (ROA) Spectroscopy for Membrane Binding Proteins
Aim 3: Prototype Combined Electronic CD / ROA Instrument for the Characterization of Membrane Binding
Proteins

## Key facts

- **NIH application ID:** 10933425
- **Project number:** 5R01GM150225-02
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Bjoern Markus Reinhard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $346,500
- **Award type:** 5
- **Project period:** 2023-09-23 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933425

## Citation

> US National Institutes of Health, RePORTER application 10933425, UV Plasmon-Enhanced Chiroptical Spectroscopy of Membrane-Binding Proteins (5R01GM150225-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10933425. Licensed CC0.

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