# Uncovering New Chemical and Physical Methods to Analyze Biological Fibrillar Nanostructures

> **NIH NIH R35** · RICE UNIVERSITY · 2024 · $375,153

## Abstract

PROJECT SUMMARY
Fibrillar nanostructures are prevalent in nature, ranging from information storage (DNA) and communication
(mRNA), to structure (collagen, amyloids) and pathology (collagen, amyloids, fibronectin). Many of these
structures (e.g., Amyloids) can have functional roles in organisms as well as participate in disease states.
These structures interact with many molecules in organisms; however, understanding these interactions is
challenging due to the need for appropriate chemical and physical tools that provide detailed fundamental
information on binding sites, dissociation constants, binding stoichiometry, and the topology of these
structures. Some of the techniques typically used by researchers give inconsistent and even erroneous results.
We are especially interested in amyloid structures since they are tough to study due to the large degree of
disorder (random-coil sidechains), making their analysis difficult using standard techniques such as NMR and
X-ray. To address these challenges, our overall goal for the next five years of research is to develop advanced
photochemical and photophysical strategies that will reveal important structural and affinity information about
biological nanofibrillar structures. The foundational work performed in our group led to the first example of a
metal dipyridophenazine complex for sensing amyloids using fluorescence spectroscopy. Later we showed that
metal complexes could be used to quantify a-synuclein nanoaggregates (a protein associated with Parkinson’s
disease) in cells. Combining biophysical and computational techniques, we proposed a site for molecular
binding in amyloid-b (between Val18 and Phe20) and a mechanism for the light-switching behavior of
ruthenium dipyridophenazine complexes. This binding site was later confirmed by selective photooxidation
(photochemical footprinting) using a rhenium complex, becoming the first experimentally confirmed binding site
in a full-length amyloid nanofibril. Ruthenium complexes were also used to detect and study soluble globular
oligomers (with high toxicity to neural cells) using fluorescence anisotropy. Currently, we have published more
than 15 papers in this area, 8 of which were published in top journals (JACS or higher); my research group has
published over 110 articles in 14 years at Rice University. Building on these advances, we will explore the use
of photochemical footprinting to elucidate binding sites in various amyloids and other fibrillar structures. We
anticipate studying dissociation constants and binding stoichiometry on fibrillar nanostructures using global
fitting of multiple saturation equations, providing a strategy to evaluate these important parameters correctly. In
the case of systems with multiple binding sites we will study the use of time-resolved spectroscopy to extract
the binding information for the different binding sites simultaneously. We will examine the rate of diffusion of
singlet oxygen as a way to determine topologi...

## Key facts

- **NIH application ID:** 10765237
- **Project number:** 1R35GM152038-01
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Angel Marti-Arbona
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,153
- **Award type:** 1
- **Project period:** 2024-03-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765237

## Citation

> US National Institutes of Health, RePORTER application 10765237, Uncovering New Chemical and Physical Methods to Analyze Biological Fibrillar Nanostructures (1R35GM152038-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10765237. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*