Peptide-Decorated DNA Nanostructures Promote Site-Specific Hydroxyapatite Growth

Abstract

The guiding principle for mineralized tissue formation is that mineral growth occurs through the interaction of Ca2+ and phosphate ions with extracellular matrix (ECM) proteins. Recently, nanoengineered DNA structures have been proposed as mimics to ECM scaffolds. However, these principles have not been applied to mineralized tissues. Here, we describe DNA nanostructures, namely, a DNA nanotube and a DNA origami rectangle that are site specifically functionalized with a mineral-promoting “SSEE” peptide derived from ECM proteins present in mineralized tissues. In the presence of Ca2+ and phosphate ions (mineralizing conditions), site-specific calcium phosphate formation occurred on the DNA nanostructures. Amorphous calcium phosphate or hydroxyapatite was formed depending on the incubation time, shape of the DNA nanostructure, and amount of Ca2+ and phosphate ions present. The ability to design and control the growth of hydroxyapatite through nanoengineered scaffolds provides insights into the mechanisms that may occur during crystal nucleation and growth of mineralized tissues and can inspire mineralized tissue regeneration strategies.

Designer, Programmable DNA‐peptide hybrid materials with emergent properties to probe and modulate biological systems

“…In the growth of mineralized tissues such as bone and teeth, certain specialised cells act as templates for the growth of hydroxyapatite through the secretion of an organic matrix [152,153] . The regeneration of these mineralized tissues depends upon the ability to mimic their complex hierarchical structures [154] .…”

“…In the growth of mineralized tissues such as bone and teeth, certain specialised cells act as templates for the growth of hydroxyapatite through the secretion of an organic matrix. [152,153] The regeneration of these mineralized tissues depends upon the ability to mimic their complex hierarchical structures. [154] Unfortunately, existing strategies have not attained much success because of a failure to control the precise location of tissue growth within a scaffold.…”

“…Interestingly, the functionalized DNA nanostructures were able to witness calcium phosphate (a key component of hydroxyapatite) growth in as little as 20 minutes, a much faster rate as compared to nonfunctionalized control groups. [153] Ignatius and coworkers developed an injectable human serum albumin-DNA hybrid hydrogel for the inhibition of osteoclast formation and activity. Owing to several advanced characteristics such as a self-healing nature, the ability to undergo stable loading and spatiotemporally release proteins, this hydrogel has potential to be an advanced treatment for bone diseases such as osteoporosis.…”

Secondary Structure of DNA Aptamer Influences Biomimetic Mineralization of Calcium Carbonate

“…DNA has been previously studied in calcium carbonate mineralization by Sommerdijk et al and by Lukeman et al with success, demonstrating mineralization inhibition and morphological control. DNA has more recently been used in relation to a number of other materials including noble metal nanoparticles, , zinc oxide, silica, − manganese pyrophosphate, calcium phosphate, − and other metal cation phosphates. − We have previously reported the SELEX identification of DNA aptamers with an ability to modulate calcium phosphate mineralization and to specifically label hydroxyapatite over amorphous calcium phosphate. , The result of these two different SELEX protocols was a host of DNA sequences with a high prevalence of G nucleotides. , Aptamer sequences from one SELEX method contained 43 ± 9% G nucleotides, and 84% of the sequences were capable of forming a G-quadruplex secondary structures . Aptamer G was identified from this pool as likely forming a G-quadruplex structure, according to computational methods and by showing an enhanced stability in the presence of potassium. , A similar selected aptamer showed evidence of G-quadruplex formation in circular dichroism studies .…”

Tuning dynamic DNA- and peptide-driven self-assembly in DNA–peptide conjugates

“…For example, peptides can benet from the rigid control of selfassembly that DNA nanotechnology provides, while DNA can be enhanced by the increased biological and mechanical stability which peptides supply. 1,7 This makes DNA-peptide conjugates ideal candidates for exploration in medicinal and therapeutic elds, 6,[8][9][10] as well as nanoscale control and assembly of bioactive materials and catalysts. 11 DNA-peptide conjugate systems have recently been rising in prominence.…”