One-Pot Synthesis of Bioinspired Peptide-Decorated Apatite Nanoparticles for Nanomedicine.

Hybrid organic-inorganic bio-inspired apatite nanoparticles (NPs) are attractive for biomedical applications and especially in nanomedicine. Unfortunately, their applications in nanomedicine are limited by their broad particle size distributions and uncontrolled drug loading due to their multistep synthesis process.  Besides, very few attempts at exposing bioactive peptides on apatite NPs are made. In this work, an original one-pot synthesis of well-defined bioactive hybrid NPs composed of a mineral core of bioinspired apatite surrounded by an organic corona of bioactive peptides is reported. Dual stabilizing-bioactive agents, phosphonated polyethylene glycol-peptide conjugates, are prepared and directly used during apatite precipitation i) to form the organic corona during apatite precipitation, driving the size and shape of resulting hybrid NPs with colloidal stabilization and ii) to expose peptide moieties (RGD or YIGSR sequences) at the NPs periphery in view of conferring additional surface properties to enhance their interaction with cells. Here, the success of this approach is demonstrated, the functionalized NPs are fully characterized by Fourier-transform infrared, Raman, X-ray diffraction, solid and liquid state NMR, transmission electron microscopy, and dynamic light scattering, and their interaction with fibroblast cells is followed, unveiling a synergistic proliferative effect.

Monitoring of CaCO3 Nanoscale Structuration through Real-Time Liquid Phase Transmission Electron Microscopy and Hyperpolarized NMR.

Calcium carbonate (CaCO3) is one of the most significant biominerals in nature. Living organisms are able to control its biomineralization by means of an organic matrix to tailor a myriad of hybrid functional materials. The soluble organic components are often proteins rich in acidic amino-acids such as l-aspartic acid. While several studies have demonstrated the influence of amino acids on the crystallization of calcium carbonate, nanoscopic insight of their impact on CaCO3 mineralization, in particular at the early stages, is still lacking. Herein, we implement liquid phase-transmission electron microscopy (LP-TEM) in order to visualize in real-time and at the nanoscale the prenucleation stages of CaCO3 formation. We observe that l-aspartic acid favors the formation of individual and aggregated prenucleation clusters which are found stable for several minutes before the transformation into amorphous nanoparticles. Combination with hyperpolarized solid state nuclear magnetic resonance (DNP NMR) and density functional theory (DFT) calculations allow shedding light on the underlying mechanism at the prenucleation stage. The promoting nature of l-aspartic acid with respect to prenucleation clusters is explained by specific interactions with both Ca2+ and carbonates and the stabilization of the Ca2+-CO32-/HCO3- ion pairs favoring the formation and stabilization of the CaCO3 transient precursors. The study of prenucleation stages of mineral formation by the combination of in situ LP-TEM, advanced analytical techniques (including hyperpolarized solid-state NMR), and numerical modeling allows the real-time monitoring of prenucleation species formation and evolution and the comprehension of their relative stability.

Formation and Evolution of Nanoscale Calcium Phosphate Precursors under Biomimetic Conditions.

Simulated body fluids (SBFs) that mimic human blood plasma are widely used media for in vitro studies in an extensive array of research fields, from biomineralization to surface and corrosion sciences. We show that these solutions undergo dynamic nanoscopic conformational rearrangements on the timescale of minutes to hours, even though they are commonly considered stable or metastable. In particular, we find and characterize nanoscale inhomogeneities made of calcium phosphate (CaP) aggregates that emerge from homogeneous SBFs within a few hours and evolve into prenucleation species (PNS) that act as precursors in CaP crystallization processes. These ionic clusters consist of ∼2 nm large spherical building units that can aggregate into suprastructures with sizes of over 200 nm. We show that the residence times of phosphate ions in the PNS depend critically on the total PNS surface. These findings are particularly relevant for understanding nonclassical crystallization phenomena, in which PNS are assumed to act as building blocks for the final crystal structure.

Collagen Suprafibrillar Confinement Drives the Activity of Acidic Calcium-Binding Polymers on Apatite Mineralization.

Bone collagenous extracellular matrix provides a confined environment into which apatite crystals form. This biomineralization process is related to a cascade of events partly controlled by noncollagenous proteins. Although overlooked in bone models, concentration and physical environment influence their activities. Here, we show that collagen suprafibrillar confinement in bone comprising intra- and interfibrillar spaces drives the activity of biomimetic acidic calcium-binding polymers on apatite mineralization. The difference in mineralization between an entrapping dentin matrix protein-1 (DMP1) recombinant peptide (rpDMP1) and the synthetic polyaspartate validates the specificity of the 57-KD fragment of DMP1 in the regulation of mineralization, but strikingly without phosphorylation. We show that all the identified functions of rpDMP1 are dedicated to preclude pathological mineralization. Interestingly, transient apatite phases are only found using a high nonphysiological concentration of additives. The possibility to combine biomimetic concentration of both collagen and additives ensures specific chemical interactions and offers perspectives for understanding the role of bone components in mineralization.

Solid-State Phase Transformation and Self-Assembly of Amorphous Nanoparticles into Higher-Order Mineral Structures.

Materials science has been informed by nonclassical pathways to crystallization, based on biological processes, about the fabrication of damage-tolerant composite materials. Various biomineralizing taxa, such as stony corals, deposit metastable, magnesium-rich, amorphous calcium carbonate nanoparticles that further assemble and transform into higher-order mineral structures. Here, we examine a similar process in abiogenic conditions using synthetic, amorphous calcium magnesium carbonate nanoparticles. Applying a combination of high-resolution imaging and in situ solid-state nuclear magnetic resonance spectroscopy, we reveal the underlying mechanism of the solid-state phase transformation of these amorphous nanoparticles into crystals under aqueous conditions. These amorphous nanoparticles are covered by a hydration shell of bound water molecules. Fast chemical exchanges occur: the hydrogens present within the nanoparticles exchange with the hydrogens from the surface-bound H2O molecules which, in turn, exchange with the hydrogens of the free H2O molecule of the surrounding aqueous medium. This cascade of chemical exchanges is associated with an enhanced mobility of the ions/molecules that compose the nanoparticles which, in turn, allow for their rearrangement into crystalline domains via solid-state transformation. Concurrently, the starting amorphous nanoparticles aggregate and form ordered mineral structures through crystal growth by particle attachment. Sphere-like aggregates and spindle-shaped structures were, respectively, formed from relatively high or low weights per volume of the same starting amorphous nanoparticles. These results offer promising prospects for exerting control over such a nonclassical pathway to crystallization to design mineral structures that could not be achieved through classical ion-by-ion growth.

Assessing the Onset of Calcium Phosphate Nucleation by Hyperpolarized Real-Time NMR.

We report an experimental approach for high-resolution real-time monitoring of transiently formed species occurring during the onset of precipitation of ionic solids from solution. This is made possible by real-time nuclear magnetic resonance (NMR) monitoring using dissolution dynamic nuclear polarization (D-DNP) to amplify signals of functional intermediates and is supported by turbidimetry, cryogenic electron microscopy, and solid-state NMR measurements. D-DNP can provide drastic signal improvements in NMR signal amplitudes, permitting dramatic reductions in acquisition times and thereby enabling us to probe fast interaction kinetics such as those underlying formation of prenucleation species (PNS) that precede solid-liquid phase separation. This experimental strategy allows for investigation of the formation of calcium phosphate (CaP)-based minerals by 31P NMR-a process of substantial industrial, geological, and biological interest. Thus far, many aspects of the mechanisms of CaP nucleation remain unclear due to the absence of experimental methods capable of accessing such processes on sufficiently short time scales. The approach reported here aims to address this by an improved characterization of the initial steps of CaP precipitation, permitting detection of PNS by NMR and determination of their formation rates, exchange dynamics, and sizes. Using D-DNP monitoring, we find that under our conditions (i) in the first 2 s after preparation of oversaturated calcium phosphate solutions, PNS with a hydrodynamic radius of Rh ≈ 1 nm is formed and (ii) following this rapid initial formation, the entire crystallization processes proceed on considerably longer time scales, requiring >20 s to form the final crystal phase.

Structural description of surfaces and interfaces in biominerals by DNP SENS.

Biological mineralized tissues are hybrid materials with complex hierarchical architecture composed of biominerals often embedded in an organic matrix. The atomic-scale comprehension of surfaces and organo-mineral interfaces of these biominerals is of paramount importance to understand the ultrastructure, the formation mechanisms as well as the biological functions of the related biomineralized tissue. In this communication we demonstrate the capability of DNP SENS to reveal the fine atomic structure of biominerals, and more specifically their surfaces and interfaces. For this purpose, we studied two key examples belonging to the most significant biominerals family in nature: apatite in bone and aragonite in nacreous shell. As a result, we demonstrate that DNP SENS is a powerful approach for the study of intact biomineralized tissues. Signal enhancement factors are found to be up to 40 and 100, for the organic and the inorganic fractions, respectively, as soon as impregnation time with the radical solution is long enough (between 12 and 24 h) to allow an efficient radical penetration into the calcified tissues. Moreover, ions located at the biomineral surface are readily detected and identified through 31P or 13C HETCOR DNP SENS experiments. Noticeably, we show that protonated anions are preponderant at the biomineral surfaces in the form of HPO42- for bone apatite and HCO32- for nacreous aragonite. Finally, we demonstrate that organo-mineral interactions can be probed at the atomic level with high sensitivity. In particular, reliable 13C-{31P} REDOR experiments are achieved in a few hours, leading to the determination of distances, molar proportion and binding mode of citrate bonded to bone mineral in native compact bone. According to our results, only 80% of the total amount of citrate in bone is directly interacting with bone apatite through two out of three carboxylic groups.

Solid-state NMR study reveals collagen I structural modifications of amino acid side chains upon fibrillogenesis.

In vivo, collagen I, the major structural protein in human body, is found assembled into fibrils. In the present work, we study a high concentrated collagen sample in its soluble, fibrillar, and denatured states using one and two dimensional {(1)H}-(13)C solid-state NMR spectroscopy. We interpret (13)C chemical shift variations in terms of dihedral angle conformation changes. Our data show that fibrillogenesis increases the side chain and backbone structural complexity. Nevertheless, only three to five rotameric equilibria are found for each amino acid residue, indicating a relatively low structural heterogeneity of collagen upon fibrillogenesis. Using side chain statistical data, we calculate equilibrium constants for a great number of amino acid residues. Moreover, based on a (13)C quantitative spectrum, we estimate the percentage of residues implicated in each equilibrium. Our data indicate that fibril formation greatly affects hydroxyproline and proline prolyl pucker ring conformation. Finally, we discuss the implication of these structural data and propose a model in which the attractive force of fibrillogenesis comes from a structural reorganization of 10 to 15% of the amino acids. These results allow us to further understand the self-assembling process and fibrillar structure of collagen.

Water-mediated structuring of bone apatite.

It is well known that organic molecules from the vertebrate extracellular matrix of calcifying tissues are essential in structuring the apatite mineral. Here, we show that water also plays a structuring role. By using solid-state nuclear magnetic resonance, wide-angle X-ray scattering and cryogenic transmission electron microscopy to characterize the structure and organization of crystalline and biomimetic apatite nanoparticles as well as intact bone samples, we demonstrate that water orients apatite crystals through an amorphous calcium phosphate-like layer that coats the crystalline core of bone apatite. This disordered layer is reminiscent of those found around the crystalline core of calcified biominerals in various natural composite materials in vivo. This work provides an extended local model of bone biomineralization.

43Ca MAS-DNP NMR of Frozen Solutions for the Investigation of Calcium Ion Complexation.

Calcium ion complexation in aqueous solutions is of paramount importance in biology as it is related to cell signaling, muscle contraction, or biomineralization. However, Ca2+-complexes are dynamic soluble entities challenging to describe at the molecular level. Nuclear magnetic resonance appears as a method of choice to probe Ca2+-complexes. However, 43Ca NMR exhibits severe limitations arising from the low natural abundance coupled to the low gyromagnetic ratio and the quadrupolar nature of 43Ca, which overall make it a very unreceptive nucleus. Here, we show that 43Ca dynamic nuclear polarization (DNP) NMR of 43Ca-labeled frozen solutions is an efficient approach to enhance the NMR receptivity of 43Ca and to obtain structural insights about calcium ions complexed with representative ligands including water molecules, ethylenediaminetetraacetic acid (EDTA), and l-aspartic acid (l-Asp). In these conditions and in combination with numerical simulations and calculations, we show that 43Ca nuclei belonging to Ca2+ complexed to the investigated ligands exhibit rather low quadrupolar couplings (with CQ typically ranging from 0.6 to 1 MHz) due to high symmetrical environments and potential residual dynamics in vitrified solutions at a temperature of 100 K. As a consequence, when 1H→43Ca cross-polarization (CP) is used to observe 43Ca central transition, "high-power" νRF(43Ca) conditions, typically used to detect spin 1/2 nuclei, provide ∼120 times larger sensitivity than "low-power" conditions usually employed for detection of quadrupolar nuclei. These "high-power" CPMAS conditions allow two-dimensional (2D) 1H-43Ca HetCor spectra to be readily recorded, highlighting various Ca2+-ligand interactions in solution. This significant increase in 43Ca NMR sensitivity results from the combination of distinct advantages: (i) an efficient 1H-mediated polarization transfer from DNP, resembling the case of low-natural-abundance spin 1/2 nuclei, (ii) a reduced dynamics, allowing the use of CP as a sensitivity enhancement technique, and (iii) the presence of a relatively highly symmetrical Ca environment, which, combined to residual dynamics, leads to the averaging of the quadrupolar interaction and hence to efficient high-power CP conditions. Interestingly, these results indicate that the use of high-power CP conditions is an effective way of selecting symmetrical and/or dynamic 43Ca environments of calcium-containing frozen solution, capable of filtering out more rigid and/or anisotropic 43Ca sites characterized by larger quadrupolar constants. This approach could open the way to the atomic-level investigation of calcium environments in more complex, heterogeneous frozen solutions, such as those encountered at the early stages of calcium phosphate or calcium carbonate biomineralization events.

Acidic Osteoid Templates the Plywood Structure of Bone Tissue.

Bone is created by osteoblasts that secrete osteoid after which an ordered texture emerges, followed by mineralization. Plywood geometries are a hallmark of many trabecular and cortical bones, yet the origin of this texturing in vivo has never been shown. Nevertheless, extensive in vitro work revealed how plywood textures of fibrils can emerge from acidic molecular cholesteric collagen mesophases. This study demonstrates in sheep, which is the preferred model for skeletal orthopaedic research, that the deeper non-fibrillar osteoid is organized in a liquid-crystal cholesteric geometry. This basophilic domain, rich in acidic glycosaminoglycans, exhibits low pH which presumably fosters mesoscale collagen molecule ordering in vivo. The results suggest that the collagen fibril motif of twisted plywood matures slowly through self-assembly thermodynamically driven processes as proposed by the Bouligand theory of biological analogues of liquid crystals. Understanding the steps of collagen patterning in osteoid-maturation processes may shed new light on bone pathologies that emerge from collagen physico-chemical maturation imbalances.

The predominant role of collagen in the nucleation, growth, structure and orientation of bone apatite.

The involvement of collagen in bone biomineralization is commonly admitted, yet its role remains unclear. Here we show that type I collagen in vitro can initiate and orientate the growth of carbonated apatite mineral in the absence of any other vertebrate extracellular matrix molecules of calcifying tissues. We also show that the collagen matrix influences the structural characteristics on the atomic scale, and controls the size and the three-dimensional distribution of apatite at larger length scales. These results call into question recent consensus in the literature on the need for Ca-rich non-collagenous proteins for collagen mineralization to occur in vivo. Our model is based on a collagen/apatite self-assembly process that combines the ability to mimic the in vivo extracellular fluid with three major features inherent to living bone tissue, that is, high fibrillar density, monodispersed fibrils and long-range hierarchical organization.

Formation of aragonitic layered structures from kaolinite and amorphous calcium carbonate precursors.

Clay materials have been an ever-present accoutrement of modern civilization; improvements to process these materials have quickened their utilization for use in complex multiaxial load-bearing structures. Specifically, with better methods to organize the constituent metal oxide components in clay, the distribution of characteristic nematic and smectic phases can be controlled. In this work, we utilize the interactions of an amorphous calcium carbonate phase with kaolinite to form a complex composite that can be organized into distinct hierarchical structures. We demonstrate that these ACC-kaolinite composites can maintain characteristic long-range-ordered layer-by-layer structures across many length scales, from nano- to millimeter, through convenient and economical processing at room temperature.

Probing the mobility of ibuprofen confined in MCM-41 materials using MAS-PFG NMR and hyperpolarised-(129)Xe NMR spectroscopy.

The continuous-flow hyperpolarised (HP)-(129)Xe NMR and magic angle spinning-pulsed field gradient (MAS-PFG) NMR techniques have been used for the first time to study the distribution and the dynamics of ibuprofen encapsulated in MCM-41 with two different pore diameters.

Strontium-driven physiological to pathological transition of bone-like architecture: A dose-dependent investigation.

Whilst strontium (Sr2+) is widely investigated for treating osteoporosis, it is also related to mineralization disorders such as rickets and osteomalacia. In order to clarify the physiological and pathological effects of Sr2+ on bone biomineralization , we performed a dose-dependent investigation in bone components using a 3D scaffold that displays the hallmark features of bone tissue in terms of composition (osteoblast, collagen, carbonated apatite) and architecture (mineralized collagen fibrils hierarchically assembled into a twisted plywood geometry). As the level of Sr2+ is increased from physiological-like to excess, both the mineral and the collagen fibrils assembly are destabilized, leading to a drop in the Young modulus, with strong implications on pre-osteoblastic cell proliferation. Furthermore, the microstructural and mechanical changes reported here correlate with that observed in bone-weakening disorders induced by Sr2+ accumulation, which may clarify the paradoxical effects of Sr2+ in bone mineralization. More generally, our results provide physicochemical insights into the possible effects of inorganic ions on the assembly of bone extracellular matrix and may contribute to the design of safer therapies for treating osteoporosis. STATEMENT OF SIGNIFICANCE: Physiological-like (10% Sr2+) and excess accumulation-like (50% Sr2+) doses of Sr2+ are investigated in 3D biomimetic assemblies possessing the high degree of organization found in the extracellular of bone. Above the physiological dose, the organic and inorganic components of the bone-like scaffold are destabilized, resulting in impaired cellular activity, which correlates with bone-weakening disorders induced by Sr2+.

Biphasic NMR of Hyperpolarized Suspensions-Real-Time Monitoring of Solute-to-Solid Conversion to Watch Materials Grow.

Nuclear magnetic resonance (NMR) spectroscopy is a key method for the determination of molecular structures. Due to its intrinsically high (i.e., atomistic) resolution and versatility, it has found numerous applications for investigating gases, liquids, and solids. However, liquid-state NMR has found little application for suspensions of solid particles as the resonances of such systems are excessively broadened, typically beyond the detection threshold. Herein, we propose a route to overcoming this critical limitation by enhancing the signals of particle suspensions by >3.000-fold using dissolution dynamic nuclear polarization (d-DNP) coupled with rapid solid precipitation. For the proof-of-concept series of experiments, we employed calcium phosphate (CaP) as a model system. By d-DNP, we boosted the signals of phosphate 31P spins before rapid CaP precipitation inside the NMR spectrometer, leading to the inclusion of the hyperpolarized phosphate into CaP-nucleated solid particles within milliseconds. With our approach, within only 1 s of acquisition time, we obtained spectra of biphasic systems, i.e., micrometer-sized dilute solid CaP particles coexisting with their solution-state precursors. Thus, this work is a step toward real-time characterization of the solid-solution equilibrium. Finally, integrating the hyperpolarized data with molecular dynamics simulations and electron microscopy enabled us to shed light on the CaP formation mechanism in atomistic detail.

Detection of biogenic amorphous calcium carbonate (ACC) formed by bacteria using FTIR spectroscopy.

While the formation of intracellular amorphous calcium carbonate (ACC) by living organisms is widespread, its detection in prokaryotes remains difficult owing to its susceptibility to transform or dissolve upon sample preparation. Because of these challenges, a large number of ACC-forming prokaryotes may have been undetected and their abundance in the natural environment is possibly underestimated. This study identifies diagnostic spectral markers of ACC-forming prokaryotes that facilitate their detection in the environment. Accordingly, ACC formed by cyanobacteria was characterized using Fourier transform infrared (FTIR) spectroscopy in near-IR, mid-IR, and far-IR spectral regions. Two characteristic FTIR vibrations of ACC, at âˆ¼ 860 cm-1and âˆ¼ 306 cm-1, were identified as reliable spectral probes to rapidly detect prokaryotic ACC. Using these spectral probes, several Microcystis strains whose ACC-forming capability was unknown, were tested. Four out of eight Microcystis strains were identified as possessing ACC-forming capability and these findings were confirmed by scanning electron microscopy (SEM) observations. Overall, our findings provide a systematic characterization of prokaryotic ACC that facilitate rapid detection of ACC forming prokaryotes in the environment, a prerequisite to shed light on the role of ACC-forming prokaryotes in the geochemical cycle of Ca in the environment.

Bio-Activation of HA/ß-TCP Porous Scaffolds by High-Pressure CO2 Surface Remodeling: A Novel "Coating-from" Approach.

Biphasic macroporous Hydroxyapatite/ß-Tricalcium Phosphate (HA/ß-TCP) scaffolds (BCPs) are widely used for bone repair. However, the high-temperature HA and ß-TCP phases exhibit limited bioactivity (low solubility of HA, restricted surface area, low ion release). Strategies were developed to coat such BCPs with biomimetic apatite to enhance bioactivity. However, this can be associated with poor adhesion, and metastable solutions may prove difficult to handle at the industrial scale. Alternative strategies are thus desirable to generate a highly bioactive surface on commercial BCPs. In this work, we developed an innovative "coating from" approach for BCP surface remodeling via hydrothermal treatment under supercritical CO2, used as a reversible pH modifier and with industrial scalability. Based on a set of complementary tools including FEG-SEM, solid state NMR and ion exchange tests, we demonstrate the remodeling of macroporous BCP surface with the occurrence of dissolution-reprecipitation phenomena involving biomimetic CaP phases. The newly precipitated compounds are identified as bone-like nanocrystalline apatite and octacalcium phosphate (OCP), both known for their high bioactivity character, favoring bone healing. We also explored the effects of key process parameters, and showed the possibility to dope the remodeled BCPs with antibacterial Cu2+ ions to convey additional functionality to the scaffolds, which was confirmed by in vitro tests. This new process could enhance the bioactivity of commercial BCP scaffolds via a simple and biocompatible approach.

Inorganic phosphate in growing calcium carbonate abalone shell suggests a shared mineral ancestral precursor.

The presence of phosphate from different origins (inorganic, bioorganic) is found more and more in calcium carbonate-based biominerals. Phosphate is often described as being responsible for the stabilization of the transient amorphous calcium carbonate phase. In order to specify the composition of the mineral phase deposited at the onset of carbonated shell formation, the present study investigates, down to the nanoscale, the growing shell from the European abalone Haliotis tuberculata, using a combination of solid state nuclear magnetic resonance, scanning transmission electron microscope and spatially-resolved electron energy loss spectroscopy techniques. We show the co-occurrence of inorganic phosphate with calcium and carbonate throughout the early stages of abalone shell formation. One possible hypothesis is that this first-formed mixed mineral phase represents the vestige of a shared ancestral mineral precursor that appeared early during Evolution. In addition, our findings strengthen the idea that the final crystalline phase (calcium carbonate or phosphate) depends strongly on the nature of the mineral-associated proteins in vivo.

Investigation of the interface in silica-encapsulated liposomes by combining solid state NMR and first principles calculations.

In the context of nanomedicine, liposils (liposomes and silica) have a strong potential for drug storage and release schemes: such materials combine the intrinsic properties of liposome (encapsulation) and silica (increased rigidity, protective coating, pH degradability). In this work, an original approach combining solid state NMR, molecular dynamics, first principles geometry optimization, and NMR parameters calculation allows the building of a precise representation of the organic/inorganic interface in liposils. {(1)H-(29)Si}(1)H and {(1)H-(31)P}(1)H Double Cross-Polarization (CP) MAS NMR experiments were implemented in order to explore the proton chemical environments around the silica and the phospholipids, respectively. Using VASP (Vienna Ab Initio Simulation Package), DFT calculations including molecular dynamics, and geometry optimization lead to the determination of energetically favorable configurations of a DPPC (dipalmitoylphosphatidylcholine) headgroup adsorbed onto a hydroxylated silica surface that corresponds to a realistic model of an amorphous silica slab. These data combined with first principles NMR parameters calculations by GIPAW (Gauge Included Projected Augmented Wave) show that the phosphate moieties are not directly interacting with silanols. The stabilization of the interface is achieved through the presence of water molecules located in-between the head groups of the phospholipids and the silica surface forming an interfacial H-bonded water layer. A detailed study of the (31)P chemical shift anisotropy (CSA) parameters allows us to interpret the local dynamics of DPPC in liposils. Finally, the VASP/solid state NMR/GIPAW combined approach can be extended to a large variety of organic-inorganic hybrid interfaces.