Structure–Activity Relationships of Hydroxyapatite-Binding Peptides

Ling, Chen; Zhao, Weilong; Wang, Ziqiu; Chen, Jiadong; Ustriyana, Putu; Gao, Min; Sahai, Nita

doi:10.1021/acs.langmuir.9b03779

Cited by 21 publications

(14 citation statements)

References 39 publications

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“…On the basis of bioinformatics, molecular dynamics, and metadynamics calculations, Zhao et al concluded that the charge density of the peptide primarily controls the binding affinity to the surface, while the secondary structure plays a minor role . More recently, on the basis of CD, binding affinity, and mineral morphology analyses, Ling et al concluded that the HAp-binding affinity is correlated with inhibition of transformation to crystalline HAp and formation of plate-like particles instead of needle-like particles . The findings of Ling et al agree well with a previously studied phage display selected HAp-binding peptide by Gungormus et al They showed that a peptide with strong binding affinity to HAp (HABP1) results in larger early spherical ACP particles and a predominantly plate-like particle morphology.…”

Section: Results and Discussionsupporting

confidence: 57%

“…41 More recently, on the basis of CD, binding affinity, and mineral morphology analyses, Ling et al concluded that the HAp-binding affinity is correlated with inhibition of transformation to crystalline HAp and formation of plate-like particles instead of needle-like particles. 42 The findings of Ling et al agree well with a previously studied phage display selected HAp-binding peptide by Gungormus et al 36 They showed that a peptide with strong binding affinity to HAp (HABP1) results in larger early spherical ACP particles and a predominantly plate-like particle morphology. However, when considering a structure−function relationship for a peptide, binding to mineral surface and promotion/inhibition of mineralization should be considered as related but separate functions.…”

Section: ■ Materials and Methodsmentioning

confidence: 94%

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Accelerated Calcium Phosphate Mineralization by Peptides with Adjacent Oppositely Charged Residues

Gungormus

Özdoğan

Ertem

et al. 2020

ACS Biomater. Sci. Eng.

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Calcium phosphate mineralizing peptides are of special importance for dental and orthopedic applications, such as caries remineralization and improved osteointegration. Uncovering the mechanism of action for such peptides is an ongoing challenge with the aim of a better fundamental understanding of biomineralization processes and developing optimized peptides for clinical use. It has recently been reported that "adjacent oppositely charged residue" motifs are found abundantly in cation binding, inorganic surface binding, or biomineralization-related proteins and may play a key role in the biomineralization events. Despite their medical importance, the role of these motifs has not yet been investigated on calcium phosphate mineral systems. To investigate this, we have designed peptides with different structural properties and different numbers of adjacent oppositely charged residues. We have evaluated their effects on in vitro calcium phosphate mineralization kinetics and mineral properties. The kinetics of the mineralization increased proportionally with an increasing number of adjacent oppositely charged residues. Two peptides with relatively high structural stability and two adjacent oppositely charged residues resulted in faster mineralization and more crystalline mineral compared to a peptide with a higher structural degree of freedom that contained only acidic residues. The fastest mineralization and the highest mineral crystallinity were obtained with a peptide containing the highest number of adjacent oppositely charged residues and highest structural degree of freedom. Our findings and observations from previously identified natural or designed peptides indicate that, in addition to structural instability, adjacent oppositely charged residues play a role in the cation binding, inorganic surface binding, and biomineralization of peptides and require further investigation. Lastly, the peptide identified in this study is an agent with potential medical applications involving the treatment of mineralized tissues.

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Section: Results and Discussionsupporting

confidence: 57%

Section: ■ Materials and Methodsmentioning

confidence: 94%

Accelerated Calcium Phosphate Mineralization by Peptides with Adjacent Oppositely Charged Residues

Gungormus

Özdoğan

Ertem

et al. 2020

ACS Biomater. Sci. Eng.

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“…In fact, both the Arg and Asp side chains of the RGD peptide are likely to participate in the binding of the Hap surface to the Fmoc-FF/S/RGD hydrogel. Molecular dynamics simulations suggest that electrostatic interactions play a dominant role in the binding of peptides and proteins to Hap surfaces and that charged groups such as carboxylate, amine or guanidine may interact with the calcium, phosphate and hydroxide ions on the Hap crystal lattice [58] , [59] , [60] . This could explain the increased mechanical properties (raise of G') observed for Fmoc-FF/S/RGD incorporating Hap compared to the other hydrogels, as shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

et al. 2022

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Hydrogels are water-swollen networks with great potential for tissue engineering applications. However, their use in bone regeneration is often hampered due to a lack of materials’ mineralization and poor mechanical properties. Moreover, most studies are focused on osteoblasts (OBs) for bone formation, while osteoclasts (OCs), cells involved in bone resorption, are often overlooked. Yet, the role of OCs is pivotal for bone homeostasis and aberrant OC activity has been reported in several pathological diseases, such as osteoporosis and bone cancer. For these reasons, the aim of this work is to develop customised, reinforced hydrogels to be used as material platform to study cell function, cell-material interactions and ultimately to provide a substrate for OC differentiation and culture. Here, Fmoc-based RGD-functionalised peptide hydrogels have been modified with hydroxyapatite nanopowder (Hap) as nanofiller, to create nanocomposite hydrogels. Atomic force microscopy showed that Hap nanoparticles decorate the peptide nanofibres with a repeating pattern, resulting in stiffer hydrogels with improved mechanical properties compared to Hap- and RGD-free controls. Furthermore, these nanocomposites supported adhesion of Raw 264.7 macrophages and their differentiation in 2D to mature OCs, as defined by the adoption of a typical OC morphology (presence of an actin ring, multinucleation, and ruffled plasma membrane). Finally, after 7 days of culture OCs showed an increased expression of TRAP, a typical OC differentiation marker. Collectively, the results suggest that the Hap/Fmoc-RGD hydrogel has a potential for bone tissue engineering, as a 2D model to study impairment or upregulation of OC differentiation. Statement of significance Altered osteoclasts (OC) function is one of the major cause of bone fracture in the most commonly skeletal disorders (e.g. osteoporosis). Peptide hydrogels can be used as a platform to mimic the bone microenvironment and provide a tool to assess OC differentiation and function. Moreover, hydrogels can incorporate different nanofillers to yield hybrid biomaterials with enhanced mechanical properties and improved cytocompatibility. Herein, Fmoc-based RGD-functionalised peptide hydrogels were decorated with hydroxyapatite (Hap) nanoparticles to generate a hydrogel with improved rheological properties. Furthermore, they are able to support osteoclastogenesis of Raw264.7 cells in vitro as confirmed by morphology changes and expression of OC-markers. Therefore, this Hap-decorated hydrogel can be used as a template to successfully differentiate OC and potentially study OC dysfunction.

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“…This process consists of multiple stages during which several intermediate calcium phosphate species are formed, leading to the formation of crystalline HAp. − This process is kinetically favorable to classical crystal nucleation, and its precursors are thermodynamically stable . However, the process is not fully understood …”

Section: Introductionmentioning

confidence: 99%

Understanding the Adhesion Mechanism of Hydroxyapatite-Binding Peptide

Duanis‐Assaf

Lavie

et al. 2022

Langmuir

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Understanding the interactions between the protein collagen and hydroxyapatite is of high importance for understanding biomineralization and bone formation. Here, we undertook a reductionist approach and studied the interactions between a short peptide and hydroxyapatite. The peptide was selected from a phage-display library for its high affinity to hydroxyapatite. To study its interactions with hydroxyapatite, we performed an alanine scan to determine the contribution of each residue. The interactions of the different peptide derivatives were studied using a quartz crystal microbalance with dissipation monitoring and with single-molecule force spectroscopy by atomic force microscopy. Our results suggest that the peptide binds via electrostatic interactions between cationic moieties of the peptide and the negatively charged groups on the crystal surface. Furthermore, our findings show that cationic residues have a crucial role in binding. Using molecular dynamics simulations, we show that the peptide structure is a contributing factor to the adhesion mechanism. These results suggest that even small conformational changes can have a significant effect on peptide adhesion. We suggest that a bent structure of the peptide allows it to strongly bind hydroxyapatite. The results presented in this study improve our understanding of peptide adhesion to hydroxyapatite. On top of physical interactions between the peptide and the surface, peptide structure contributes to adhesion. Unveiling these processes contributes to our understanding of more complex biological systems. Furthermore, it may help in the design of de novo peptides to be used as functional groups for modifying the surface of hydroxyapatite.

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Structure–Activity Relationships of Hydroxyapatite-Binding Peptides

Cited by 21 publications

References 39 publications

Accelerated Calcium Phosphate Mineralization by Peptides with Adjacent Oppositely Charged Residues

Accelerated Calcium Phosphate Mineralization by Peptides with Adjacent Oppositely Charged Residues

Hydroxyapatite-decorated Fmoc-hydrogel as a bone-mimicking substrate for osteoclast differentiation and culture

Understanding the Adhesion Mechanism of Hydroxyapatite-Binding Peptide

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