# Structural, spatial, and temporal features guiding amelogenins transformation of calcium phosphate into enamel

> **NIH NIH R01** · BATTELLE PACIFIC NORTHWEST LABORATORIES · 2024 · $477,873

## Abstract

Project Summary
The goal of the proposed work is to develop a molecular level, structural understanding of the role of
amelogenin in directing the hierarchical growth of enamel. Enamel is one of the hardest biominerals known,
and is hierarchically structured to prevent crack propagation, allowing it to last many people a lifetime.
However, naturally occurring diseases or damage do occur to enamel and our current therapies fall far short of
nature made enamel. Over the past decade we have come to understand that amelogenin assembles into
quaternary structures as oligomers containing 12 proteins, units which further assemble into nanospheres.
These assemblies, the molecular level interactions governing them, their interactions with calcium phosphate,
and their role in mineral phase transformations, are not well understood for enamel formation. We do know
that the protein amelogenin, the predominant protein in the forming enamel milieu, is critical in formation
based on amelogenin null mouse models showing severely damaged enamel phenotypes. Protein structure
often dictates function, yet we have only begun to reveal the structure of amelogenin. Further, the mineral in
the enamel milieu begins as ions, and transitions through an amorphous stage prior to becoming elongated,
crystallized HAP needles. Both in vivo and in vitro studies have demonstrated that amelogenin controls this
phase transformation process, but the structural, spatial, and temporal aspects of this process are not
understood. In our proposed work, we bring a set of advanced characterization techniques to an in vitro system
simulating developing enamel to evaluate the structure of amelogenin when interacting with calcium
phosphates, to understand the spatial distribution of amelogenin around developing calcium phosphate mineral
ribbons, and to develop a molecular level view of the transformation process from calcium phosphate clusters,
through the amorphous phase, on to crystalline HAP. This suite of techniques has never been brought to bear
on understanding the challenge of enamel growth and will result in an understanding of the development of
enamel that is currently lacking. The results of this work are relevant to biomineralization systems in general
and may ultimately inform more robust therapeutics for enamel replacements.

## Key facts

- **NIH application ID:** 10894309
- **Project number:** 5R01DE015347-17
- **Recipient organization:** BATTELLE PACIFIC NORTHWEST LABORATORIES
- **Principal Investigator:** Wendy J Shaw
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $477,873
- **Award type:** 5
- **Project period:** 2021-08-19 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894309

## Citation

> US National Institutes of Health, RePORTER application 10894309, Structural, spatial, and temporal features guiding amelogenins transformation of calcium phosphate into enamel (5R01DE015347-17). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894309. Licensed CC0.

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