Biomedical Engineering Reference
In-Depth Information
to Asp6 and the acute step is strong, so these peptides should accelerate the velocity
of the acute step preferentially. However, when the crystal unit is incorporated into
the crystal surface, the structured water that binds to the crystal surface and crystal
unit must be removed. Calculations using a semi-empirical quantum mechanical
model revealed that when Asp3 to Asp6 is used, more water molecules on the crystal
surface at the acute step must be removed
.
This indicates that they more effectively
accelerate growth in the obtuse step.
Elhadj et al. also analyzed the effect of various Asp-containing peptides and
proteins on the step velocity of a growing calcite face (104) [
56
]. Growth was
accelerated with all molecules at low concentrations (Fig.
4.2
). Examination of
the acceleration rate and net molecular charge of the individual peptides revealed a
clear correlation between the degree of net molecular charge and the crystal growth
rate; however, the correlation was not perfect. For example, the AP7-N (aragonitic
protein N-terminal domain molecular weight 7 kDa; [
57
]), which contains many
hydrophobic amino acids, deviates from this correlation. This indicates that, in ad-
dition to the net molecular charge, the degree of hydrophilicity and hydrophobicity
of the additives also affects the crystal growth rate. In fact, when the hydrophilicity-
hydrophobicity of peptides used for the experiment was measured and compared
with the crystal growth rate, a clear correlation was obtained. The hydrophilic
molecules apparently enhanced the dehydration of the crystal face and crystal unit
and thereby accelerated crystal growth.
Osteopontin is involved in the crystal growth of calcium oxalate monohydrate
(COM) as well as of HAP [
58
]. COM is a component of kidney stones. Since
urine is supersaturated with respect to COM, kidney stones are formed if COM
deposition and kidney stone growth are not regulated. Osteopontin is one of the
proteins that possess this inhibitory function. Grohe et al. derived peptide-containing
phosphorylated serines and acidic amino acids (pSHEpSTEQSDAIDpSAEK) from
the osteopontin sequence and prepared three synthetic peptides—one with three
phosphates (P3), one with one phosphate (P1), and one with no phosphates (P0)—
and investigated their interaction with COM [
59
]. All three peptides adsorbed to the
COM (100) surface and inhibited crystal growth, with stronger inhibitory effects
seen as the number of phosphates increased. Simulation using molecular dynamics
showed that the binding to the (100) surface was achieved in the order of P3, P1,
and P0. The Asp-12 and Glu-15 of the C-terminus of the P0 peptide were separated
from the crystal surface upon binding. The P1 peptide as a whole was close to the
crystal surface; however, amino acids from Gln-7 to Asp-12 in the middle of the
peptide were slightly distant from the surface. All amino acids in the P3 peptide
were close to the crystal surface. The amino acids in the P1 and P3 peptides closest
to the crystal surface were aspartic acids and glutamic acids, but not phosphorylated
serines. Grohe et al. suggested that the phosphate group has the ability to stabilize
the interaction of crystals and peptides by drawing entire peptide molecules to
the crystal surface [
59
]. When crystals were grown in the presence of P3 and P1
peptides, the COM crystal morphology was transformed into a dumbbell shape. P0
does not affect the morphology [
60
].
