How Charged Amino Acids Regulate Nucleation of Biomimetic Hydroxyapatite Nanoparticles on the Surface of Collagen Mimetic Peptides: Molecular Dynamics and Free Energy Investigations

Tan, Xiaohui; Xue, Zhiyu; Zhu, Hua; Wang, Xin; Xu, Dingguo

doi:10.1021/acs.cgd.0c00353

Cited by 19 publications

(35 citation statements)

References 91 publications

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“…39 The electrostatic interaction between the positively charged argnine residue and PO4 3ion could regulate the HA nucleation process by the arginine residue of collagen. 40 The distribution of postively and negatively charged groups at the CaP cluster surface could be correlated with the zeta potential experiments in the following subsection. Zeta potential was used to estimate the average surface electronegativities.…”

Section: Aggregation Of Cap Clusters In Aqueous and Sbf Solutionsmentioning

confidence: 90%

“…The regulation of nucleation process of CaP by the charged amino acids of collagen surface was demonstrated by CHARMM27 based MD study in solution. [38][39][40] Neutral amino acids of collagen such as glycine and hydroxyproline residues, whose carboxylate groups were also found to be freely accessible to the Ca 2+ ions based on generalized AMBER force field. 41 The interactions between lysine and HA (100) surface was ascribed to the dominant electrostatic interaction in Ca-O ionic bonding, followed by hydrogen bonding between Cε-H/amine-H and phosphate-O.…”

Section: Introductionmentioning

confidence: 99%

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Tuning Coordination Modes and Nucleation of Calcium Phosphate with Oligomeric Lactic Acid and pH Values: Theoretical and Experimental Study

Chen

Guo

et al. 2021

Preprint

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Mineralization of calcium phosphate (CaP) is ubiquitous in nature, which can facilitate biological organisms produce hierarchically structured minerals. The influences of the addition of oligomeric lactic acid (LACn, n=1, 8) and changing pH values on nucleation processes of CaP under the simulated body fluid (SBF) solution or aqueous solution were revealed by using ab initio molecular dynamics (AIMD) and molecular dynamics (MD) simulations. Through increasing pH value, the coordination between differently protonated phosphate species and Ca2+ ions could be tuned from the monodentate (η1) to the coexisting monodentate and bidentate (η2) modes. The carboxyl and hydroxyl groups of LAC molecules are capable of forming multiple interactions such as proton transfer, electrostatic interaction, and intermolecular hydrogen bonding with phosphate species and Ca2+ ions on both pre-nucleation clusters and hydroxyapatite (HA) surfaces. The high-throughput experimentations (HTE) with factors of the adding LAC, changing Ca/P ratios (1.25 ~ 2.50), using different solutions demonstrated that the UV-Vis absorbance values decreased with addition of LAC, indicating the inhibition of the nucleation process of CaP. At the physiological pH of 7.4, the CaP samples with different Ca/P ratios (1.50, 1.67 and 2.00) exhibited negative zeta potential values, which were correlated with the surface electrostatic potential distributions and potential biological applications. The precipitation was CaHPO4·2H2O (DCPD) in neutral condition at the early stage of nucleation process. Understanding the effects of different pH and Ca/P values on the nucleation process and interfacial interaction between LAC additive and the nanocluster is helpful to guide the rational design of biocompatible materials.

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Section: Aggregation Of Cap Clusters In Aqueous and Sbf Solutionsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Tuning Coordination Modes and Nucleation of Calcium Phosphate with Oligomeric Lactic Acid and pH Values: Theoretical and Experimental Study

Chen

Guo

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…If, during characterization, such changes are detected, consider changing the location of the functional handle (e.g., middle vs end of peptide) or the functional handle identity. Use of molecular dynamic simulations to evaluate the location that will have the least impact on peptide properties may also be of value. − Difficulties visualizing sample . There are a number of reasons sample visualization may be challenging, including poor labeling, low sample concentration, and assembled peptide structure size.…”

Section: Methods 4: Peptide Structure Visualization Within a Hydrogelmentioning

confidence: 99%

Rapid Production of Multifunctional Self-Assembling Peptides for Incorporation and Visualization within Hydrogel Biomaterials

Ford

Kloxin

2021

ACS Biomater. Sci. Eng.

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Peptides are of continued interest for therapeutic applications, from soluble and immobilized ligands that promote desired binding or uptake to self-assembled supramolecular structures that serve as scaffolds in vitro and in vivo. These applications require efficient and scalable synthetic approaches because of the large amounts of material that often are needed for studies of bulk material properties and their translation. In this work, we establish new methods for the synthesis, purification, and visualization of assembling peptides, with a focus on multifunctional collagen mimetic peptides (mfCMPs) relevant for formation and integration within hydrogel-based biomaterials. First, a methodical approach useful for the microwave-assisted synthesis of assembling peptide sequences prone to deletions was established, beginning with the identification of the deleted residues and their locations and followed by targeted use of dual chemistry couplings for those specific residues. Second, purification techniques that integrate the principles of heating and ion displacement with traditional chromatography and dialysis were implemented to improve separation and isolation of the desired multifunctional peptide product, which contained blocks for thermoresponsiveness and ionic interactions. Third, an approach for fluorescent labeling of these mfCMPs, which is orthogonal to their assembly and their covalent incorporation into a bulk hydrogel material, was established, allowing visualization of the resulting hierarchical fibrillar structures in three dimensions within hydrogels using confocal microscopy. The methods presented in this work allow the production of multifunctional peptides in scalable quantities and with minimal deletions, enabling future studies for better understanding of composition−structure−property relationships and for translating these biomaterials into a range of applications. Although mfCMPs are the focus of this work, the methods demonstrated could prove useful for other assembling peptide systems and for the production of peptides more broadly for therapeutic applications.

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“…If the cells were pretreated with chlorpromazine (clathrin-pathway inhibitor) ( Shi et al, 2017 ) or NaN 3 (ATP inhibitor), ( Ryan et al, 2015 ) the uptake of HAp were significantly prohibited, indicating clathrin-mediated and ATP-dependent endocytosis for HAp nanoparticles. The physicochemical properties of HAp as well as its interactions with proteins (such as collagen) or substrates have also been extensively studied at atomic level ( Cheng et al, 2017 ; Wang et al, 2018b ; Wang et al, 2018c ; Liu et al, 2018 ; Xie et al, 2018 ; Gu et al, 2019 ; Xue et al, 2019 ; Liu et al, 2020 ; Ma et al, 2020 ; Tan et al, 2020 ; Wang et al, 2020 ). However, only a few studies have reported the clathrin-mediated adhesion and endocytosis of HAp, ( Shi et al, 2017 ; Shi et al, 2018 ; Huang et al, 2020 ) while the molecular details remain elusive.…”

Section: Introductionmentioning

confidence: 99%

The Morphology of Hydroxyapatite Nanoparticles Regulates Cargo Recognition in Clathrin-Mediated Endocytosis

Zhu

Zhou

Liu

et al. 2021

Front. Mol. Biosci.

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The clathrin-associated protein adaptin-2 (AP2) is a distinctive member of the hetero-tetrameric clathrin adaptor complex family. It plays a crucial role in many intracellular vesicle transport pathways. The hydroxyapatite (HAp) nanoparticles can enter cells through clathrin-dependent endocytosis, induce apoptosis, and ultimately inhibit tumor metastasis. Exploring the micro process of the binding of AP2 and HAp is of great significance for understanding the molecular mechanism of HAp’s anti-cancer ability. In this work, we used molecular modeling to study the binding of spherical, rod-shaped, and needle-shaped HAps toward AP2 protein at the atomic level and found that different nanoparticles’ morphology can determine their binding specificity through electrostatic interactions. Our results show that globular HAp significantly changes AP2 protein conformation, while needle-shaped HAP has more substantial binding energy with AP2. Therefore, this work offers a microscopic picture for cargo recognition in clathrin-mediated endocytosis, clarifies the design principles and possible mechanisms of high-efficiency nano-biomaterials, and provides a basis for their potential anti-tumor therapeutic effects.

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How Charged Amino Acids Regulate Nucleation of Biomimetic Hydroxyapatite Nanoparticles on the Surface of Collagen Mimetic Peptides: Molecular Dynamics and Free Energy Investigations

Cited by 19 publications

References 91 publications

Tuning Coordination Modes and Nucleation of Calcium Phosphate with Oligomeric Lactic Acid and pH Values: Theoretical and Experimental Study

Tuning Coordination Modes and Nucleation of Calcium Phosphate with Oligomeric Lactic Acid and pH Values: Theoretical and Experimental Study

Rapid Production of Multifunctional Self-Assembling Peptides for Incorporation and Visualization within Hydrogel Biomaterials

The Morphology of Hydroxyapatite Nanoparticles Regulates Cargo Recognition in Clathrin-Mediated Endocytosis

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