is one of the mysteries of biology: How does tooth
enamel, the hardest mineral in the mammalian body,
emerge from soft, organic gum tissue?
important part of the answer appears in a report in
the latest issue of Science.
puzzle of enamel formation centers on amelogenin,
a protein secreted by cells in gum tissue called ameloblasts.
Amelogenin's closest analogue in the human body is
collagen, the protein that guides the formation of
mineral in bone.
collagen - which remains an essential part of bone
structure, helping it to heal after fractures - amelogenin
degrades and disappears during the process of enamel
mineral growth, or biomineralization.
its transient role makes it hard to study, amelogenin
has not been well understood despite investigations
stretching over many years, said Janet Moradian-Oldak,
a professor in the University of Southern California
School of Dentistry and the paper's lead author. USC
Postdoctoral research associate Chang Du contributed
to the paper.
its nature, amelogenin cannot form a lasting platform
or scaffold for enamel development. The question is:
can a protein with a very short life span provide
a reliable structure for biomineralization?
answer is yes, according Oldak and her team, whose
discovery was serendipitous.
researchers, in collaboration with Giuseppe Falini
at the Universita di Bologna in Italy, had been attempting
to study amelogenin by crystallizing it. Crystallography
is a traditional method of exploring molecular structure.
a year, the researchers were unable to obtain amelogenin
crystals. Instead, their efforts produced what looked,
under a microscope, like long, fettucine-like fibers.
The fibers consisted of chains of amelogenin nanospheres:
tiny balls of amelogenin molecules.
called the fibers "microribbons." She was
struck by the similarity in structure between the
ribbons and the calcium hydroxy apatite crystals that
make up the bulk of enamel.
apatite crystals in enamel are highly elongated, with
a length to width ratio as high as 1000. The microribbons'
chains of amelogenin nanospheres were also elongated.
wondered if the microribbons might be the scaffold
for biomineralization she had been looking for. It
was a leap that her scientific training told her was
excessively optimistic. "I think what you need
is a bit of imagination to be able to link these things,"
the researchers mineralized the ribbons and dipped
them into calcium phosphate solution, they obtained
aligned and organized apatite crystals similar to
those found in enamel. The microribbons had functioned
perfectly as a scaffold.
work was done in vitro, but studies of the literature
turned up observations of similar structures in vivo,
including a report of "beaded rows" of amelogenin
nanospheres alongside developing crystals in enamel.
demonstrate that amelogenin protein has a strong tendency
to assemble in linear arrays of nanospheres, and we
propose that this property is a key to its function
as a scaffolding protein during the early stage of
enamel mineralization," the researchers wrote.
finding unlocks one mystery of enamel formation and
may have long-term applications.
artificial enamel is a decades-old goal among researchers
in dental science and, more generally, in the medical-device
community. As a filling material, enamel has the potential
to outperform less durable substances such as composites
and silver-mercury alloys. Medical-device developers
are constantly searching for durable natural materials
to use in place of titanium and plastic parts.
in vitro self-assembly system of Du et al will be
a useful guide to the development of biomimetic structures,"
wrote Arthur Veis, professor of cell and molecular
biology at Northwestern University in the perspective
companion to the Science paper.
have shown that minerals can develop within protein
and synthetic polypeptide gels, but a scaffold was
necessary to provide long-range order. In contrast,
Du et al show that the self-assembly of the amelogenin
nanospheres, and their further assembly into nanosphere
arrays, forms its own scaffold that can direct the
alignment of the mineral crystallites."
research was supported by the National Institute of
Dental and Craniofacial Research, part of the National
Institutes of Health.
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