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Calcium-Induced Molecular Rearrangement of Peptide Folds Enables Biomineralization of Vaterite Calcium Carbonate Hao Lu, Helmut Lutz, Steven J Roeters, Matthew A. Hood, Arne Schäfer, Rafael Muñoz-Espí, Rüdiger Berger, Mischa Bonn, and Tobias Weidner J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b00281 • Publication Date (Web): 08 Feb 2018 Downloaded from http://pubs.acs.org on February 11, 2018
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Calcium-Induced Molecular Rearrangement of Peptide Folds Enables Biomineralization of Vaterite Calcium Carbonate Hao Lu,†,* Helmut Lutz,† Steven J. Roeters,§ Matthew A. Hood,† Arne Schäfer,† Rafael MuñozEspí,†,‡ Rüdiger Berger,† Mischa Bonn† and Tobias Weidner†,§,* †
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany
‡
Institute of Materials Science (ICMUV), Universitat de València, C/ Catedràtic José Beltrán 2, 46980 Paterna, Spain
§
Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark
Supporting Information ABSTRACT: Proteins can control mineralization of CaCO3 by selectively triggering the growth of calcite, aragonite or vaterite phases. The templating of CaCO3 by proteins must occur predominantly at the protein/CaCO3 interface, yet molecular-level insights into the interface during active mineralization have been lacking. Here, we investigate the role of peptide folding and structural flexibility on the mineralization of CaCO3. We study two amphiphilic peptides based on glutamic acid and leucine with β−sheet and α−helical structures. While both sequences lead to vaterite structures, the β−sheets yield free-standing vaterite nanosheet with superior stability and purity. Surfacespectroscopy and molecular dynamics simulations reveal that reciprocal structuring of calcium ions and peptides lead to the effective synthesis of vaterite by mimicry of the (001) crystal plane.
Calcium carbonate (CaCO3) is the most abundant mineral on earth. Besides geological CaCO3, the mineral also plays an 1-3 important role for life. CaCO3 is a key component of the shell and skeleton of mollusk, mussels, sponges and other marine life. The biogenesis of CaCO3-containing hard tissue is tightly controlled by proteins, which have been shown to exert control over the nucleation and growth of different 4-10 phases of CaCO3. Of the three CaCO3 minerals calcite, aragonite and vaterite, the latter is thermodynamically unstable and occurs rarely as a biomineral component. At the same time, vaterite has desirable properties for applications in drug delivery, implant design, surface coating and 11 nanofabrication. The mimicry of protein controlled and stabilized CaCO3 formation with desired phase selection such as vaterite has been the white whale in the biomineral 12 community for decades. For biomimetic design approaches, it is important to understand how proteins can steer the growth of mineralized CaCO3 structures at the molecular 4-5, 7-9 level. Proteins involved in CaCO3 biogenesis are often enriched in acidic amino acids, such as glutamic (Glu) and aspartic 8, (Asp) acids, and structured into ordered β−sheet domains. 13-14 So far, the most accepted hypothesis states that negative2+ ly charged Glu and Asp sites are structured to template Ca
14-18 16, 19-
ions into a lattice that initiates the growth of CaCO3. 21
Yet the mechanism of the crystallization of CaCO3 remains poorly understood. Gebauer et al. propose that the mineralization of CaCO3 proceeds via prenucleation of metastable 22-24 CaCO3 clusters. Gower et al. propose that CaCO3 mineral25 ize through liquid precursors. Experiments to study these mechanisms have primarily been focused on the mineral side, and less on the peptide structures and their registry on a specific crystal phase, the peptide structure during mineralization of CaCO3 is unknown.
Scheme 1. Molecular structure and representation of the LE10 and LLE10 peptides synthesized.
To determine the role of peptide structure and the molecular interaction with CaCO3 precursors, we probe here the very interface of peptides and ions and during mineral growth using surface-sensitive vibrational sum frequency generation (SFG) spectroscopy and molecular dynamic (MD) simulations. We study two model peptide sequences, composed exclusively of leucine (L) and glutamic acid (E) residues, E(LE)9 and E(LLE)9, abbreviated as LE10 and LLE10, respectively (Scheme 1). In analogy to positively charged 26 lysine-leucine ‘LK’ peptides, the hydrophobic periodicity of LE10 and LLE10 is chosen to drive peptide folding into β−strand and helical secondary structures at the air-water interface. The acidic residues (∼50% for LE10 and∼33% for 2+ LLE10) should provide strong affinity to Ca ions, potentially resulting in CaCO3 mineralization after HCO3 addition. In the following, we first show the influence of the amino acid
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sequence on the stabilization of vaterite at interfaces and then explain the underlying mechanism by surface spectroscopy and computer simulations. For the experiments, LE10 and LLE10 are allowed to selfassemble at the air-water interface. Following injection of CaCO3 precursors below the peptide film (see SI for details), both peptides trigger the nucleation of CaCO3 films. The films were lifted off the water surface using a gold-coated silicon wafer piece and then studied ex-situ. While the films span the entire surface, larger CaCO3 structures with morphologies typically found in vaterite, grow out of the film. 27 (Fig. S2), similar to what has been observed for copolymers. X-ray diffraction confirmed the vaterite phase of CaCO3 (see Fig. S1). The LE10 sample contained 99% ±1% vaterite. While previous studies have already shown that the local enrich3, 28ment of acidic residues can promote vaterite over calcite, 30 31 such a high selectivity has rarely been reported. The LLE10 peptide shows substantially lower vaterite content (34%±4% vaterite).
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in SPS (s-polarized SFG, p-polarized VIS, s-polarized IR) polarization combination, which is sensitive to both backbone and Glu side chain modes. The spectra of LE10 peptides -1 exhibit bands at ∼1570 cm , assigned to the asymmetric COO stretching vibration mode from the deprotonated Glu 38-39 -1 side-chains, and at ∼1615 cm , usually assigned to the 40-42 amide B2 mode of β−sheet backbone. The amide-I spec-1 trum of LLE10 displays a peak near 1640 cm , suggesting a 40, 43 helical structure. The presence of distinct peaks shows that the peptide structures are well-defined at the interface. 2+ The spectra change after Ca coordination: for the β−sheet -1 LE10 peptide, the intensity of the amide-I peak at ∼1615 cm -1 increases; also the intensity of the peak at ∼1570 cm increases slightly. The enhancement of two peaks also occurs for -1 LLE10. In addition, a shoulder near 1670 cm , attributed to a 40-41, 44 small β−turn or β−sheet contribution, is observed. For both peptides the spectral features remain largely unchanged during the further mineralization reaction with HCO3 . We therefore conclude that the conformational change of the backbones and side chains must occur during the initial 2+ peptide−Ca interaction. Spectra measured with the SSP polarization combination (Fig. 2, panel c and d), which show only the backbone amideI band without interference from side chain bands, allow an undisturbed view on the reorientation of the peptides. In agreement with the SPS spectra, the intensity increases upon 2+ interaction with Ca ions (see Table S3−S6), indicating a 2+ refolding process induced by Ca . The change in alignment is also apparent from the changes in the CH spectral region (Fig. S7).
Figure 1. (a) SEM image of the CaCO3 mineral nanosheet formed by LE10 peptides. The nanosheet is free-standing when spanning the holes of the TEM grid. The red arrows indicate a rapture in the sheet. (b) TEM shows nanopores in the sheet, approximately ∼2 nm in diameter; inset: pore size distribution. The film stabilities are also markedly different. While LE10-mineralized films could be lifted off with TEM grids and showed freestanding sheets, which were intact over tens of micrometers, LLE10 did not form freestanding films. Fig. 1 presents electron microscopy images for the LE10 sheets (see SI for scanning force microscopy images). X-ray photoelectron spectroscopy (XPS) analysis showed that the LE10– CaCO3 sheets had a thickness of ∼1.9 nm (Table S1). The nanosheets have pores with a diameter of 2.1±0.4 nm, similar to carbon sheets prepared from lipids and self-assembled 32-33 monolayers. XPS spectra and depth profiling revealed a molecular composition in line with intact peptides and CaCO3 and that peptides are evenly distributed throughout the film (Fig. S42+ 6). The Ca to Glu side chain ratio was determined to be ∼1.4 2+ for LE10 and ∼0.5 for LLE10 (see Table S2). The lower Ca coordination number for LLE10 is likely related to the lower film stability compared with the LE10–CaCO3 sheets. To shed light on the different biomineralization behavior, we investigated the peptide structure during mineralization using SFG spectroscopy. SFG selection rules dictate that signal originates only from ordered molecules at interfaces, 34-37 without contributions from bulk molecules. Fig. 2 presents spectra in the amide-I region at different stages: in 2+ phosphate-buffered saline, after Ca coordination, and after CaCO3 mineralization. Panels a and b show spectra recorded
Figure 2. SPS and SSP SFG spectra along with fits for LE10 (a, c) and LLE10 (b, d) peptides at air-water interface (black), 2+ after Ca coordination (red), and after CaCO3 mineralization (blue). Calculated amide I spectra in the lower part of each panel match well with experimental data. 2+
To investigate how the interaction with Ca affects the peptides, we ran MD simulations. Simulations were set up 2+ with and without Ca ions. Each simulation contained a box with 12 peptides (see SI for details). Fig. 3 a, b shows final
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snapshots of the simulations, with and without Ca , after a simulation time of 500 ns. The LE peptides show a significant β−sheet content, which changes into a strongly curved, hair2+ pin-like β−turn structure upon addition of Ca ions. The expected helical folding of the LLE peptides remains largely 2+ unchanged upon interaction with Ca , while it did result in some loss of β−turn structure. Differential Ramachandran 2+ plots (Fig. 3 c, d) verify that, upon interaction with Ca , LE10 changes to a loop and hairpin-like structure while for the LLE10 peptides an increase of the helical content but no significant refolding is apparent. Ostensibly, the LE10 peptide has more structural freedom to respond to the presence 2+ of Ca ions. To test whether the MD simulations are in agreement with the SFG results, we calculated theoretical SFG spectra directly from snapshots of the simulation. The calculated spectra, also shown in Fig. 2, are in good agreement with the experimental data and reproduce the band positions, spectral shapes and intensity increases of the experimental spectra well. The agreement of calculation and experiment lends credence to the MD results. To analyze the peptide structure in more detail, especially the side chain–ion interface, we have determined the
spacing is reduced to ca. 3.1 Å (see Fig. S13 for Ca tion).
2+
ion loca-
This compaction is likely driven by the higher valency of 2+ calcium ions. The correlation of Ca and Glu spacing may indicate that the Glu groups are mainly located at the bridge 2+ and hollow sites with respect to a hexagonal Ca interfacial 2+ lattice. Fig. 3f shows a model of a Glu-Ca registry consistent with the data. This view is in agreement with the work of Cölfen, Gebau22-23, 47-48 er et al., who hypothesize that the formation of vaterite is dictated by interacting side chains, guiding prenu2+ 2cleation of metastable CaCO3 (n Ca CO3 ) clusters and vaterite growth afterward. The important new observation here is that biomineralization of vaterite is not a static, oneway process – it is a dynamic, reciprocal mechanism where 2+ Ca ions template the side chain structure and vice versa 2+ (self-templating) – Ca steers the peptide and side chain 2+ structure into a lattice, which, in turn, templates the Ca ions into the 4.1 Å lattice resembling the vaterite (001) hexagonal lattice. The results are consistent with the formation of liquid precursors between the peptides and the calcium ions that eventually yield proto-vaterite (presumably amorphous) CaCO3, prior to formation of macrocrystalline va49 terite phases. The observed impact on vaterite formation is not specific to the peptides discussed here but rather a general characteristic of ß-strand and α-helical peptides. Section 10 of the SI summarizes a series of experiments with additional L and E containing peptides of varying lengths, folds and charge, as well as aspartic acid. The data verify that a variety of ßstrands effectively produce vaterite while helical and unstructured motifs produce less stable films with high calcite content. 2+
Figure 3. (a-b) Snapshots of MD simulations after 500 ns for LE10 (a) and LLE10 (b), respectively. Both simulations were + 2+ set up with either K (left panel) or Ca counterions (right panel). Color coding: Yellow, extended β−strand; green, β−turn; silver, random coil; purple, α−helix; blue, 310 helix; cyan, calcium ions. (c-d) Difference of Ramachandran plots 2+ with and without Ca extracted from the last 55 ns of the 2+ simulation. (e) RDF for Ca ions (left) and Glu side chains 2+ with and without Ca . (f) Proposed model for hexagonal vaterite registry by Glu sites.
2+
radial distribution functions (RDF) for the Ca ions and Glu sites (Fig. 3 e). The calcium ions show a spacing of 4.1 Å, which perfectly matches the Ca lattice in vaterite with hex45-46 agonal symmetry, but is significantly smaller than dis3 tances observed for aragonite and calcite. The Glu side chain RDF shows how vaterite is templated. Before mineralization, 2+ the smallest Glu spacing is 4 Å. When divalent Ca ions + replace the monovalent K ions at the interface, the Glu
The similarity of the Glu and Ca spacing for LE10 and LLE10 is remarkable in view of their structural dissimilarity and their differing ability to stabilize vaterite sheets. As can be seen in the MD snapshots, the strand-like LE10 peptides are structurally more flexible to ‘curl up’ and adapt more closely to the vaterite registry than the rigid LLE10 helices. This trend is also evident for the additional LE sequences discussed in the SI. This flexibility is likely explained by the larger amino acid distances in ß-strands compared with α helices. This flexibility may cause the slightly larger 2+ amount of coordinated Ca but may also lead to longerrange ordering beyond the first coordination level. Together these factors form the molecular basis underlying the frequently observed success of ß-sheet peptides in vaterite 19 formation. This study describes a promising new avenue towards peptide driven mineral design. We show that appropriate peptide folding and side-chain chemistry can lead to exceptionally stable, freestanding and nanometer thin porous vaterite sheets with potential in filter technology, single molecule 32 detection, and drug release . For biomimetic mineral architectures, it will be important to optimize the peptide structure in the context of the bidirectional nature of biomineralization where the mineral– peptide interface is structurally interrelated.
ASSOCIATED CONTENT Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website. Details of the experiments, simulation, and spectra calculation; more characterization data: XRD, SEM, SFM, XPS, depth profiling, SFG spectra and fitting parameters; additional L/E peptide mineralization experiments. (PDF)
AUTHOR INFORMATION Corresponding Author *
[email protected] *
[email protected] Notes The authors declare no competing financial interests.
ACKNOWLEDGMENT The authors thank Elke Muth, Sabine Pütz, Dr. Sapun Parekh for the assistance with the peptide synthesis, Michael Steiert for XRD measurements, Helma Burg for SFM measurements, and Gunnar Glasser and Katrin Kirchhoff for support in SEM and TEM measurements. T.W. thanks the Aarhus University Research Foundation (AUFF) and the Deutsche Forschungsgemeinschaft (WE4478/4-1) for financial support. R.B. acknowledges the support of the DFG (BE 3286/4-1). R.M.E. thanks the Spanish Ministry of Economy, Industry and Competitiveness through a Ramón y Cajal grant (grant No. RYC-2013-13451) the Max Planck Society for funding of the Max Planck Partner Group at the University of Valencia.
References: 1.Sebastiani, F.; Wolf, S. L. P.; Born, B.; Luong, T. Q.; Cölfen, H.; Gebauer, D.; Havenith, M. Angew. Chem. Int. Ed. 2017, 56, 490–495. 2.Sviben, S.; Gal, A.; Hood, M. A.; Bertinetti, L.; Politi, Y.; Bennet, M.; Krishnamoorthy, P.; Schertel, A.; Wirth, R.; Sorrentino, A.; Pereiro, E.; Faivre, D.; Scheffel, A. Nat. Commun. 2016, 7, 11128. 3.Morse, J. W.; Arvidson, R. S.; Luttge, A. Chem. Rev. 2007, 107, 342381. 4.Suzuki, M.; Saruwatari, K.; Kogure, T.; Yamamoto, Y.; Nishimura, T.; Kato, T.; Nagasawa, H. Science 2009, 325, 1388-1390. 5.Aizenberg, J.; Lambert, G.; Weiner, S.; Addadi, L. J. Am. Chem. Soc. 2002, 124, 32-39. 6.Mann, S. Biomineralization: Principles and Concepts in Bioinorganic Materials Chemistry; Oxford University Press: New York, 2001. 7.Levi, Y.; Albeck, S.; Brack, A.; Weiner, S.; Addadi, L. Chem.-Eur. J. 1998, 4, 389-396. 8.Falini, G.; Albeck, S.; Weiner, S.; Addadi, L. Science 1996, 271, 6769. 9.Belcher, A. M.; Wu, X. H.; Christensen, R. J.; Hansma, P. K.; Stucky, G. D.; Morse, D. E. Nature 1996, 381, 56-58. 10.Lowenstam;, H. A.; Weiner, S., On Biomineralization. Oxford University Press: Oxford, 1989. 11.Trushina, D. B.; Bukreeva, T. V.; Kovalchuk, M. V.; Antipina, M. N. Mat. Sci. Eng. C-Mater 2014, 45, 644-658. 12.Mao, L. B.; Gao, H. L.; Yao, H. B.; Liu, L.; Cölfen, H.; Liu, G.; Chen, S. M.; Li, S. K.; Yan, Y. X.; Liu, Y. Y.; Yu, S. H. Science 2016, 354, 107110. 13.Fu, G.; Qiu, S. R.; Orme, C. A.; Morse, D. E.; De Yoreo, J. J. Adv. Mater. 2005, 17, 2678-2683. 14.Weiner, S.; Traub, W. Febs Lett. 1980, 111, 311-316. 15.Murai, K.; Kinoshita, T.; Nagata, K.; Higuchi, M. Langmuir 2016, 32, 9351-9359. 16.Cavalli, S.; Popescu, D. C.; Tellers, E. E.; Vos, M. R. J.; Pichon, B. P.; Overhand, M.; Rapaport, H.; Sommerdijk, N. A. J. M.; Kros, A. Angew. Chem. Int. Edit. 2006, 45, 739-744. 17.Kahlen, J.; Peter, C.; Donadio, D. Cryst. Eng. Comm 2015, 17, 68636867.
Page 4 of 5
18.Raiteri, P.; Demichelis, R.; Gale, J. D.; Kellermeier, M.; Gebauer, D.; Quigley, D.; Wright, L. B.; Walsh, T. R. Faraday Discuss. 2012, 159, 61-85. 19.Chevalier, N. R.; Chevallard, C.; Goldmann, M.; Brezesinski, G.; Guenoun, P. Cryst. Growth. Des. 2012, 12, 2299-2305. 20.Jain, A.; Jochum, M.; Peter, C. Langmuir 2014, 30, 15486-15495. 21.Gong, H. F.; Yang, Y.; Pluntke, M.; Marti, O.; Majer, Z.; Sewald, N.; Volkmer, D. Dalton Trans. 2014, 43, 16857-16871. 22.Gebauer, D.; Kellermeier, M.; Gale, J. D.; Bergstrom, L.; Cölfen, H. Chem. Soc. Rev. 2014, 43, 2348-2371. 23.Gebauer, D.; Volkel, A.; Cölfen, H. Science 2008, 322, 1819-1822. 24.Smeets, P. J. M.; Cho, K. R.; Kempen, R. G. E.; Sommerdijk, N. A. J. M.; De Yoreo, J. J. Nat. Mater. 2015, 14, 394-399. 25.Gower, L. B.; Odom, D. J. J. Cryst. Growth 2000, 210, 719-734. 26.Degrado, W. F.; Lear, J. D. J. Am. Chem. Soc. 1985, 107, 7684-7689. 27.Gao, Y. X.; Yu, S. H.; Guo, X. H. Langmuir 2006, 22, 6125-6129. 28.Njegic-Dzakula, B.; Falini, G.; Brecevic, L.; Skoko, Z.; Kralj, D. J. Colloid Interf. Sci. 2010, 343, 553-563. 29.Krattiger, P.; Nassif, N.; Volkel, A.; Mastai, Y.; Wennemers, H.; Cölfen, H. Colloids Surf., A 2010, 354, 218-225. 30.Hood, M. A.; Landfester, K.; Muñoz-Espí, R. Cryst. Growth Des. 2014, 14, 1077-1085. 31.Pouget, E. M.; Bomans, P. H. H.; Goos, J. A. C. M.; Frederik, P. M.; de With, G.; Sommerdijk, N. A. J. M. Science 2009, 323, 1455-1458. 32.Turchanin, A.; Golzhauser, A. Adv. Mater. 2016, 28, 6075-6103. 33.Anselmetti, D.; Golzhauser, A. Angew. Chem. Int. Edit 2014, 53, 12300-12302. 34.Shen, Y. R., The Principles of Nonlinear Optics. J. Wiley: New York, 1984. 35.Lambert, A. G.; Davies, P. B.; Neivandt, D. J. Appl. Spectrosc. Rev. 2005, 40, 103-145. 36.Roy, S.; Covert, P. A.; FitzGerald, W. R.; Hore, D. K. Chem. Rev. 2014, 114, 8388-8415. 37.Ding, B.; Jasensky, J.; Li, Y.; Chen, Z. Acc. Chem. Res. 2016, 49, 1149−1157. 38.Paszti, Z.; Guczi, L. Vib. Spectrosc. 2009, 50, 48-56. 39.Mudunkotuwa, I. A.; Minshid, A. A.; Grassian, V. H. The Analyst 2014, 139, 870-881. 40.Nguyen, K. T.; King, J. T.; Chen, Z. J. Phys. Chem. B 2010, 114, 8291-8300. 41. Singh, B. R. Infrared Analysis of Peptides and Proteins: Principles and Applications; Singh, B. R, Eds.; ACS symposium series 750; American Chemical Society: Washington, 2000; 750, 1-190. 42.Lutz, H.; Jaeger, V.; Berger, R.; Bonn, M.; Pfaendtner, J.; Weidner, T. Adv. Mater. Interfaces 2015, 2, 15002821-7. 43.Lutz, H.; Jaeger, V.; Bonn, M.; Pfaendtner, J.; Weidner, T. J Pept Sci 2017, 23, 141-147. 44.Lutz, H.; Jaeger, V.; Schmuser, L.; Bonn, M.; Pfaendtner, J.; Weidner, T. Angew. Chem. Int. Edit 2017, 56, 8277-8280. 45.Kabalah-Amitai, L.; Mayzel, B.; Kauffmann, Y.; Fitch, A. N.; Bloch, L.; Gilbert, P. U. P. A.; Pokroy, B. Science 2013, 340, 454-457. 46.Kamhi, S. Acta Crystallogr. 1963, 16, 770-772. 47.Sun, S. T.; Chevrier, D. M.; Zhang, P.; Gebauer, D.; Cölfen, H. Angew. Chem. Int. Edit 2016, 55, 12206-12209. 48.Rao, A.; Berg, J. K.; Kellermeier, M.; Gebauer, D. Eur. J. Mineral 2014, 26, 537-552. 49.Cartwright, J. H. E.; Checa, A. G.; Gale, J. D.; Gebauer, D.; SainzDiaz, C. I. Angew. Chem. Int. Edit 2012, 51, 11960-11970.
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