Biomimetic Crystallization of l-Cystine Hierarchical Structures - Crystal

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Biomimetic Crystallization of L‑Cystine Hierarchical Structures Michal Ejgenberg and Yitzhak Mastai* Department of Chemistry and the Institute of Nanotechnology, Bar-Ilan University, Ramat-Gan 52900 Israel ABSTRACT: The origin of crystalline complex superstructures of biomaterials and the unique selfassembly mechanisms of their formations have attracted a great deal of attention recently. In this paper the crystallization of cystine hierarchical structures by a crystallization procedure that mimics the slow oxidation chemistry of L-cysteine to L-cystine is studied. The crystalline superstructures of cystine are identified by X-ray diffraction (XRD), micro Raman spectroscopy, and scanning electron microscopy (SEM). It is found that the formation of unique spherical or hexagonal shaped cystine hierarchical structures depends on the initial concentration of L-cysteine. A possible mechanism based on the self-assembly process of cystine crystals is proposed. Overall our study suggests that it is possible to control morphogenesis and the formation of cystine crystalline superstructures by a simple chemical method that mimics biomineralization.

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INTRODUCTION Biomineralization is a complex process by which organisms form minerals and is frequently associated with a high degree of regulation on different hierarchical levels. The high level of regulation depends on chemical control of precipitation and crystallization.1 Generally, biomineralization can be divided into two fundamentally different classes based on the degree of biological control exerted. In the first class, termed “biologically controlled mineralization”,2−4 the organism directly controls the mineralization process, producing minerals of selected size, morphology, structure, and orientation. This control can be achieved by various modes, including space confinement, formation of organic matrix frameworks, ion input control, construction of nucleation sites, crystal orientation and growth control, and termination of crystal growth. An additional biomineralization class, known as “biologically induced mineralization”,5−7 is characterized by the crystallization of minerals via simple interactions between organisms and their environment. It is well-known that crystallization conditions such as saturation level, temperature, pH, ionic strength (common ion effect), and reactant concentration have a great impact on the crystallization mechanism and ultimately on the crystal morphology. Therefore it is clear that biological systems need to fine-tune crystallization parameters in order to control crystal morphology and crystal polymorphism. In this regard, organisms can produce complexation agents which control supersaturation levels, achieving control over nucleation. Another example for this approach is the control over ion concentration achieved by enzymes. The tremendous effect of the crystallization conditions on the crystallization outcome has also been demonstrated in biomimetic crystallization studies. For example, Han et al. 8 showed that pH and CaCl 2 concentration have a marked influence on the polymorphism and morphology of CaCO3 crystals. At high pHs, irregular vaterite aggregates were formed, whereas at pH = 9, spherical particles of different sizes were formed. In addition, at low CaCl2 concentrations vaterite crystals were precipitated and the © 2012 American Chemical Society

proportion of calcite and the size of the particles increased with an increase in CaCl2 concentration. Control over the reactant concentration also plays a very important role in crystallization. This can be achieved in different ways such as controlling the decomposition of crystallization precursors or by catalysts such as enzymes. The decomposition of precursor molecules is widespread in several strategies for CaCO3 crystallization. The most wellknown is the ammonium carbonate decomposition method, which is temperature dependent.9 Reactant concentrations can also be controlled by redox chemistry. This is especially valid for iron and other heavy metal minerals, as soluble Fe2+ salts can be (partly) oxidized to form sparingly soluble iron oxide minerals like magnetite, maghemite, akagenite, iron oxyhydroxide, ferrihydrite, and many others.10 In this study we report the biomimetic crystallization of cystine by redox chemistry. It is known that the cysteine to cystine oxidation occurs in aqueous solutions in the presence of oxygen and trace amounts of metal ions, e.g., Cu2+ and Mg2+.11 In view of the above we have designed a crystallization setup for cystine based on the slow oxidation of cysteine to cystine, thereby mimicking biological control over saturation levels of cystine. The redox reaction can be controlled by pH and temperature. The study of the crystallization of cystine is a critical step in the pathogenesis of cystine kidney stones12,13 and is therefore of high biological importance. The formation of cystine stones is the result of an autosomal recessive disorder caused by mutations in one of two genes.14 These genes encode two parts of a transporter protein which is responsible for reabsorbing cystine and other dibasic amino acids into the bloodstream after they have been filtered by the kidneys. Mutations in either of these genes cause excessive amounts of these amino acids in the urine. Because of the low solubility of cystine, cystine crystals Received: July 8, 2012 Revised: August 28, 2012 Published: September 5, 2012 4995

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cylindrical quartz cell (5 mL, L = 50 mm) at room temperature. The Lcystine concentration (M) was calculated using the following equation: ([α]CL)L‑cysteine + ([α]CL)L‑cystine = α, where [α] = specific light rotation, C = concentration in gr/mL, L = cell length, and α = light rotation angle (observed in polarimeter). [α] L-Cysteine =-9.66°, [α] L-cystine =260°, L = 0.5 dm and CL‑cysteine + CL‑cystine = the initial concentration of L-cysteine solution.

which aggregate into stones are formed. Most recently, Ward et al.15 showed that L-cystine dimethylester and L-cystine methylester can be used to dramatically reduce the growth velocity of the six symmetry-equivalent {1,0,0} of cystine crystals due to specific binding at the crystal surfaces. In addition it should be mentioned that Ward et al.15 showed that the crystallization of L-cystine in the presence of L-cysteine as an inhibitor (in low concentrations of up to 10% of L-cysteine) significantly decreases cystine crystal sizes but does not change the crystallization yield, that is to say that L-cysteine cannot be used for the prevention of cystine kidney stones. In this paper we will demonstrate that the crystallization of cystine under biomimetic conditions results in unique spherical, flower-like, or hexagonal shaped crystalline superstructures of cystine. We will propose a mechanism for the formation of these hierarchically crystalline superstructures based on the three-dimensional assembly of cystine microsized crystals. Generally our study suggests that it is possible to control morphogenesis and superstructure formation by a simple chemical method that mimics biomineralization.

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RESULTS AND DISCUSSION In the first stage of our research we studied the cysteine to cystine oxidation kinetics. The kinetics can be studied using a variety of techniques. In this work we chose to use optical polarimetry since cysteine and cystine are both optically active, but their specific optical rotations differ greatly ([α]L‑cysteine = −9.66, [α]L‑cystine = +260). Therefore, the cysteine to cystine transformation can be monitored using optical activity measurements. In order to study the cysteine to cystine transformation rate, aqueous cysteine solutions of 0.22 M and 55 mM concentrations were prepared and their optical activity was monitored at room temperature as a function of time. Figure 1 presents the change in cystine concentration in

EXPERIMENTAL SECTION

All chemicals used were of analytical grade and were used as received without any further purification. L-Cystine (purity (TLC) ≥ 98%) and L-cysteine (purity (TLC) ≥ 97%) were purchased from Sigma Aldrich and Mica surfaces were purchased from Electron Microscopy Sciences (EMS). Double distilled water was used for the preparation of aqueous solutions for crystallization. All chemicals were used directly without any further purification. Crystallization Experiments. Bulk Crystallization. L-Cystine Crystallization. L-Cystine (4.2 mM) was dissolved in H2O by adding NaOH (pH = 11) and stirring at room temperature. The solution was then neutralized to pH = 7 using HCl(aq). Crystallization occurred after a few hours (ca. 2 h). L-Cysteine Crystallization. L-Cysteine was added to H2O (1.6 M). The solution was heated to 80 °C and stirred until the L-cysteine was completely dissolved. The solution was left to cool to room temperature and then placed in the refrigerator (4 °C). Crystals appeared overnight. Biomimetic Crystallization. All crystallization experiments were performed with double distilled water of a typical electrical conductivity of 10 μS/cm. L-Cystine Hierarchical Crystallization. Aqueous L-cysteine solutions of various concentrations were prepared (as mentioned above) by dissolving L-cysteine in water (1.1 M, 0.22 M, 55 mM, 27 mM, and 11 mM) at 80 °C. The resulting solutions were then left to cool to room temperature. The solutions were divided in two and placed in 50 mL centrifuge vials. A mica surface was added into each solution. Solutions of L-cysteine with concentrations of 1.1 M, 0.22 M, 55 mM, 27 mM, and 11 mM were placed in the refrigerator (4 °C) and at room temperature for crystallization. The crystallization was monitored daily. After observing crystallization in solutions and on the mica surfaces the mica surfaces and crystals from solutions were collected and examined by various techniques. Characterization Techniques. Scanning electron microscope (SEM) images were obtained with a FEI instrument − Inspect S model at acceleration voltages of 5 kV, 15 kV, and 30 kV. Powder Xray diffraction patterns of L-cysteine and L-cystine were acquired with a Bruker AXS D8 Advance diffractometer with Cu Kα (λ = 1.5418 Å) operating at 40 kV/40 mA. Data were collected from 10° to 50° with a step size of 0.01°. Raman measurements were acquired with a Jobin Yvon Micro Raman (model HR800, λ = 633 nm) using different objectives. AFM measurements were acquired with an ICON Bruker operating in tapping mode at room temperature. The AFM image size was 2.5 μm × 2.5 μm, scan rate = 0.3 Hz, and samples/line = 512. Optical activity measurements were acquired with a JASCO digital polarimeter (model P-1010 λ = 589 nm ± 0.005° accuracy) using a

Figure 1. Cysteine to cystine oxidation kinetics as measured by optical activity for a solution of 0.22 M of cysteine at room temperature.

solution as a function of time obtained from the optical activity measurements for a cysteine solution of 0.22 M concentration. As is observed the cysteine to cystine transformation is linear with time and the rate of cysteine to cystine oxidation is calculated to be 0.01 mM/h. The above results confirm our assumption that cysteine slowly transforms to cystine by an oxidation process in aqueous solutions. On the basis of the literature this oxidation process is driven by the presence of oxygen and trace amounts of metal ions in aqueous solutions. In this paper we define the crystallization of cystine under these conditions, namely, crystallization by the slow oxidation of cysteine to cystine as biomimetic crystallization while the crystallization of cystine and cysteine from supersaturated solutions is referred to as bulk crystallization. The next phase of our research involved exploring the mechanism of crystallization and the effects of the biomimetic crystallization conditions on the crystal morphology. For this purpose cysteine and cystine were first crystallized from bulk supersaturated solutions, as described in the Experimental Section. The crystal morphology of cysteine crystals crystallized from bulk solution is shown in Figure 2A. The crystals have a needle-like morphology with an average crystal size of 2 mm × 4996

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depend on the initial cysteine concentrations and the crystallization temperatures. On the basis of the SEM results, the biomimetic crystallization will be divided into two ranges with respect to the initial cysteine concentration. The first range, termed the “high concentration” range, includes superstructures crystallized from cysteine concentrations above 0.11 M and the second range, termed the “low concentration range”, includes superstructures crystallized from cysteine concentrations below 0.11 M. In addition, we will focus on two main aspects: first, the hierarchical order of the superstructures and second, the superstructure building block morphology, namely, the morphology of the crystals that make up the superstructures. It should be mentioned that the crystalline superstructures of cystine crystallized at room temperature and those crystallized at 4 °C are very similar. Therefore, the discussion of the results will mainly focus on cystine superstructures crystallized at room temperature. SEM images of cystine superstructures crystallized at room temperature from “high concentration” solutions are shown in Figures 2C  for cystine crystallized from 1.1 M cysteine solution concentrations and 2D for 0.22 M cysteine solution concentrations. As is evident in both cases, the crystalline superstructures are flower-shaped and composed of ultrathin sheet-like cystine crystals. The superstructures crystallized from 1.1 M solutions display typical crystal sizes of 40 μm × 40 μm, while those crystallized from 0.22 M solutions exhibit crystal sizes of about 100 μm × 100 μm. The crystalline superstructure images of cystine crystallized at room temperature from “low concentration” solutions appear in Figure 2E−G, which present structures crystallized from 55 mM, 27 mM, and 11 mM cysteine solution concentrations. It is clear that slight crystallographic orientations of the crystals exist in all three structures. Furthermore, the individual crystals composing the superstructures are ultra thick compared to the sheet-like crystals seen for the “high concentration” crystalline structures. The crystalline superstructures crystallized from 55 mM and 11 mM solutions are spherical in shape and are about 200 and 600 μm in diameter, respectively. Structures crystallized from 27 mM are hexagonal-shaped with a size of 100 μm × 100 μm. In view of the SEM results, a general trend is observed. The thickness of the cystine crystals which compose the crystalline superstructures increases as the initial cysteine concentration decreases. In order to confirm our assumption that under biomimetic conditions only cystine crystallizes, we performed detailed structure characterization of the hierarchical crystalline structures. In Figure 3, the X-ray diffraction spectra of cystine crystallized from bulk supersaturated solutions and cystine crystallized under biomimetic conditions are presented. The Xray diffraction of pure cystine crystallized under bulk conditions corresponds to the hexagonal polymorph reported in the literature,16 with space group P6122 and cell parameters a = 5.42 Å, b = 5.42 Å, c = 56.28 Å, α = β = 90° ≠ γ = 120°. Bulk cystine reveals main intense X-ray diffraction peaks at 2θ = 18.9° and 2θ = 28.5°, corresponding to the (0 0 12) and (0 0 18) planes. The X-ray diffraction spectra of the various cystine superstructures, shown in Figures 3B−D, also exhibit typical Lcystine spectra. Micro Raman studies of the hierarchical structures of cystine were also performed. Cystine and cysteine have different molecular vibrations, and therefore they can be distinguished using micro-Raman. The Raman spectra of bulk cysteine, bulk

Figure 2. Scanning electron microscopy images of cysteine crystals (A) and cystine crystals (B) crystallized from bulk supersaturated solutions and hierarchical structures of cystine crystallized at room temperature under biomimetic conditions from initial cysteine solution concentrations of 1.1 M (C), 0.22 M (D), 55 mM (E), 27 mM (F), and 11 mM (G).

500 μm. Cystine crystals crystallized under bulk conditions are shown in Figure 2B and exhibit typical hexagonal morphology with an average crystal size of 100 × 100 μm. Scanning electron microscopy (SEM) images of cystine crystallized under biomimetic conditions are shown in Figure 2C−G. As can be seen in the SEM images, the crystallization of cystine under biomimetic conditions results in the formation of superstructures which display a dramatic change in crystal morphology from cystine crystallized under bulk conditions. Furthermore, the crystal morphology and superstructure shape 4997

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Figure 3. X-ray diffraction spectra of cystine crystals (A) crystallized from bulk supersaturated solutions and hierarchical structures crystallized at room temperature under biomimetic conditions from initial cysteine solution concentrations of 1.1 M (B), 0.22 M (C), and 55 mM (D).

Figure 5. AFM image revealing the well ordered crystalline layered structure of individual crystals composing the hierarchical structures crystallized from 1.1 M L-cysteine solutions. The crystalline layered thickness is found to be around 10 nm (image size 1 μm × 1 μm).

cystine, and cystine crystallized under biomimetic conditions appear in Figure 4. The Raman spectrum of cysteine (Figure

solution. The AFM image was taken from an individual crystal. As can be seen, the AFM image displays well ordered periodicity of individual crystals attached through their {006} faces. The average thickness of the individual layers calculated from AFM line scanning is found to be 10 nm. Similar AFM results were observed for other crystalline superstructures. As mentioned above, cystine was also crystallized at low temperature (4 °C) and led to the formation of crystalline superstructures. In most cases, the morphologies of the superstructures crystallized at low temperature were identical to those crystallized at room temperature. However, superstructures crystallized from an initial L-cysteine solution concentration of 1.1 M at low temperature showed a major difference in crystal morphology. Superstructures crystallized at room temperature from 1.1 M concentrations are hexagonal shaped with a typical size of 40 μm × 40 μm while those crystallized at low temperature are sphere shaped with a typical diameter of 20 μm (Figure 6). However we have to emphasize that in both cases namely the crystallization at room temperature and at low temperature the crystalline superstructure morphology is composed of individual cystine crystal plates attached through their plate face.

Figure 4. Micro-Raman spectra of cysteine crystals (A) and cystine crystals (B) crystallized from bulk supersaturated solutions and microRaman spectra of the hierarchical structures crystallized at room temperature under biomimetic conditions from initial cysteine solution concentrations of 1.1 M (C), 0.22 M (D), and 55 mM (E).

4A) contains a peak at 2545 cm−1, which corresponds to the S− H group stretching frequency. This typical peak is absent in the cystine Raman spectrum. In contrast, the cystine Raman spectrum (Figure 4B) contains a peak at 497 cm−1, associated with the stretching frequency of the S−S bond. Raman spectra of the various cystine superstructures (Figure 4C−E) also exhibit typical vibrational spectra of cystine with strong S−S vibrations at 497 cm−1. Furthermore, none of the spectra show the presence of cysteine, leading to the conclusion that the crystalline superstructures contain only cystine. AFM was utilized to gain detailed information on the structure of the cystine hierarchical structures. As shown in the SEM images, the superstructures are composed of cystine crystals which self-assemble into highly ordered structures. Therefore, AFM could be used to study the crystalline order within these crystals. Figure 5 presents an AFM image of cystine superstructures crystallized from a 1.1 M cysteine

Figure 6. Cystine hierarchical structures crystallized from 1.1 M aqueous cysteine solutions at low temperature. 4998

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Figure 7. SEM images of cystine crystallized in the presence of cysteine (cystine/cysteine = 1/1). Cysteine acts as an additive.

Figure 8. (A) Predicted crystal morphology of cystine in a vacuum according to the attachment energy model and (B) predicted crystal morphology of cystine crystallized in the presence of cysteine.

additives in the solution and partly on interactions between the crystals. Overall, the formation of crystal superstructures is based on the formation of nanocrystals with a specific crystallographic orientation and morphology, followed by selfassembly of the nanocrystals into superstructures or mesostructures with well-defined directions. In view of the above we decided to study the formation of cystine crystalline superstructures focusing on the nucleation of cystine microsized crystals and their self-assembly into superstructures. From the optical measurements it is observed that the cysteine to cystine transformation is a slow process and approximately 10 days are required to achieve cystine supersaturation levels. From these observations we conclude that the first step in the formation of cystine superstructures is the slow nucleation of cystine crystals. It should be mentioned that at this stage of nucleation we observe a significant modification in the cystine crystal morphology compared to that of the bulk crystallization of cystine. The main crystal morphology change is manifested in a large change in the cystine crystal aspect ratio. We define the cystine crystal aspect ratio as the ratio between the length of the {006} crystal face and the length of the {11̅0} crystal face and it is calculated from the SEM images. On the basis of this definition, the change in cystine crystal morphology under various crystallization conditions can be compared. Under bulk crystallization a crystal aspect ratio of 5 is observed while for biomimetic

In summary, our results prove the formation of unique spherical or hexagonal shaped superstructures of cystine. On the basis of these results it is possible to develop a molecular mechanism for understanding the formation of cystine superstructures crystallized under biomimetic conditions. However, before discussing our proposed mechanism, we will briefly review other suggested mechanisms for the formation of crystal superstructures and mesocrystals. Recently, it was found that many crystallization processes can result in the formation of crystal superstructures via interactions of crystalline intermediates and precursor particles and through the selfassembly of nanostructured crystals.17−20 The formation of crystal superstructures has been reported for many inorganic systems, including iron oxide, cerium oxide and copper oxide21,22 and for several organic systems.23,24 In spite of the large number of superstructure crystallizations, the mechanism for the formation of the superstructures is yet unknown. Nevertheless, all papers in this research area consider the formation of crystal superstructures to be due to a crystal mediated crystallization process. In general, three types of formation mechanisms were suggested in the literature. The first one is based on interactions between the crystals and polymers or organic substances existing in the crystallizing solution. Another mechanism is based solely on the interactions between the crystals themselves and the third mechanism is based partly on interactions between crystals and polymers or 4999

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peptides, proteins, or other organic substances. However, the self-assembly of the crystals can also be based solely on the interactions between the crystals themselves. It is clear that in our crystallization system the driving force for the formation of superstructures is due to intrinsic interactions between the cystine microcrystals. Our proposed scenario for the formation of the superstructures is based on molecular interactions between the basal crystal planes of the hexagonal cystine, namely, the (006) and (006̅) crystal planes. These two planes expose acid and amine functional groups at their surface. Therefore, we assume that the strong interaction between these planes is due to electrostatic or hydrogen bonding. Overall, our proposed mechanism is in line with the general mechanism proposed for the formation of superstructures and mesocrystals. Finally we should emphasize that cysteine can strongly influence crystal morphology and can reduce the size of individual cystine crystals. Still, it is clear that cysteine cannot prevent the crystallization of “kidney cystine stones” as also reported in ref 15. Understanding the crystallization process and rationally designing crystal morphology, namely, crystal engineering, are of fundamental and practical interest. New discoveries related to our understanding of crystallization have recently emerged and have fundamentally changed our views on processes involved in crystallization and morphology control of crystals. In this paper the crystallization of cystine superstructures under chemical conditions that mimic biomimetic crystallization is described. Unlike many examples in the literature regarding the formation of crystalline superstructures in which designed additives such as polymers and biological macromolecules are employed, in our work the crystallization of cystine superstructures is achieved by simple biomimetic crystallization. Furthermore, our crystalline superstructures are formed by the self-assembly of organic microsized crystals and not of nanocrystalline particles. Nevertheless, it is shown by SEM, X-ray diffraction, and micro-Raman measurements that our cystine superstructures are composed of well-separated platelete-like shaped crystals that assemble into three-dimensional superstructures with slightly crystallographic orientation. On the basis of these results, a formation mechanism is proposed for the cystine superstructures. The underlying principles of the interaction of primary micro crystals into larger superstructures are probably due to strong interactions between the (0 0 6) and (0 0 6̅) crystal faces due to electrostatic and hydrogen binding. Our research emphasizes the importance of crystal face interactions in the formation of crystalline superstructures. This work demonstrates that crystalline superstructures of organic crystals can be crystallized by simple crystalline systems that mimic biomineralization. We believe that this work enhances the understanding of biomineralization crystallization and may help to explore principles and mechanisms for the formation of crystalline superstructures and mesocrystals.

conditions the crystal aspect ratio changes dramatically to a value of 50. Our assumption is that the large modification in the crystal aspect ratio is due to the presence of a high concentration of cysteine during cystine crystallization. In other words, in the biomimetic crystallization cysteine acts as a molecular additive that modifies the crystal morphology of cystine. In order to confirm this assumption we performed bulk cystine crystallization experiments in the presence of cysteine. A bulk cystine crystallization solution (4.1 mM, 30 mL) was prepared and 15 mg (4.1 mM) of cysteine was added into the crystallization solution. The SEM images of cystine crystallized in these experiments is shown in Figure 7. The SEM images reveal flowerlike bunches of hexagons similar to the cystine hierarchical structures, confirming our assumption on the role of cysteine as a molecular additive that modifies the crystal morphology of cystine. It is important to mention that crystallization of cysteine to cystine alone takes a number of days, and therefore we ruled out the possibility that the cysteine which is added as an additive actually crystallizes into cystine. With the intention of better understanding the effect of cysteine on cystine crystal morphology, molecular simulations of cystine crystallized in the presence of cysteine were performed. The simulations were carried out using ACCELRYS MS MODELING software using the COMPASS27 forcefield. The crystal structure of cystine was taken from the Cambridge crystallographic database (ref code LCYSTI10). Figure 8A displays the predicted crystal morphology of cystine according to the attachment energy model. This morphology is in good agreement with the observed experimental morphology of cystine crystallized in water under bulk crystallization conditions. The effect of cysteine on the crystal morphology of cystine is also simulated with the attachment energy model. The binding energies of cysteine onto the main crystal faces of cystine are calculated and the values are shown in Table 1. Table 1. Attachment Energies, Binding Energies and New Attachment Energies for the {0,0,6} and {1,1̅,0} Crystal Planes crystal planes

Eatt (kcal/mol)

Eb (kcal/mol)

new Eatt (kcal/mol)

{0,0,6} {1,1̅,0}

96 387

15 62

24 290

Next, the new attachment energy (Eatt) is calculated for each of the cystine crystal faces with a correction term originating from the binding energy of cysteine to the different faces. Figure 8B displays the crystal morphology of cystine generated with the new attachment energies (in the presence of cysteine). In addition, the aspect ratio can be calculated using the molecular simulations. For pure cystine the crystal aspect ratio calculated from the simulations is 2, while for cystine crystallized in the presence of cysteine the crystal aspect ratio is ca. 10. These results agree with our experiential observations and confirm our assumption that cysteine acts as an additive that modifies the crystal aspect ratio of cystine. The next important stage is the self-assembly and organization of the cystine microcrystals into superstructures. Most models proposed in the literature for the formation of superstructures or mesostructures are based on the selfassembly of crystals with well-defined crystallographic orientation. As was mentioned, the origin of interactions between the crystals that leads to the formation of crystal superstructures often comes from well designed additives such as polymers,

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest. 5000

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ACKNOWLEDGMENTS M.E. would like to acknowledge the BIU President’s scholarship and the ministry of science and technology program for the promotion of women in science and technology for funding.

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REFERENCES

(1) Meldrum, F. C.; Colfen, H. Chem. Rev. 2008, 108, 4332. (2) Lowenstam, H. A.; Weiner, S. On Biomineralization; Oxford University Press: New York, 1989; 324. (3) Lowenstam, H. A. Science 1981, 211, 1126. (4) Mann, S. Struct. Bonding (Berlin) 1983, 54, 125. (5) McConnaughey, T. A. Biomineralization mechanisms. In Origin, Evolution and Modern Aspects of Biomineralization in Plants and Animals; Crick, R. E., Ed.; Plenum Press: New York, 1989; p 57. (6) Bazylinski, D. A.; Frankel, R. B. Rev. Mineral. Geochem. 2003, 54, 217. (7) Weiner, S.; Dove, P. M. Rev. Mineral. Geochem. 2003, 54, 1. (8) Han, Y. S.; Hadiko, G.; Fuji, M.; Takahashi, M. J. Cryst. Growth 2006, 289, 269. (9) Gehrke, N.; Colfen, H.; Pinna, N.; Antonietti, M.; Nassif, N. Cryst. Growth Des. 2005, 5, 1317. (10) Schwertmann, U.; Cornell, R. M. Iron oxides in the Laboratory; Wiley-VCH: Weinheim, Germany, 2000. (11) Rehder, D. S.; Borges, C. R. Biochemistry 2010, 49, 7748. (12) Crawhall, J. C.; Watts, R. W. E. Am. J. Med 1968, 45, 736. (13) Palacin, M.; Borsani, G.; Sebastio, G. Curr. Opin. Genet. Dev. 2001, 11, 328. (14) Mattoo, A.; Goldfarb, D. S. Semin. Nephrol. 2008, 28, 181. (15) Rimer, J. D.; An, Z.; Zhu, Z.; Lee, M. H.; Goldfarb, D. S.; Wesson, J. A.; Ward, M. D. Science 2010, 330, 337. (16) Oughton, B. M.; Harrison, P. M. Acta Crystallogr. 1959, 12, 396. (17) Colfen, H.; Antonietti, M. Mesocrystals and Nonclassical Crystallization; John Wiley & Sons, Ltd.: Chichester, 2008. (18) Colfen, H.; Antonietti, M. Angew. Chem., Int. Ed. 2005, 44, 5576. (19) Jian-Wei, L.; Hai-Wei, L.; Shu-Hong, Y. Chem. Rev. 2012, 112, 4770−4799. (20) Jeian-Wei, L.; Shao-Yi, Z.; Hao, Q.; Wu-Cheng, W.; Shu-Hong, Y. Small 2012, 8, 2412−2420. (21) Oaki, Y.; Imai, H. Adv. Funct. Mater. 2005, 15, 1407. (22) Zhou, L.; O’Brien, P. Small 2008, 4, 1566. (23) Wohlrab, S.; Pinna, N.; Antonietti, M.; Colfen, H. Chem.Eur. J. 2005, 11, 2903. (24) Medina, D. D.; Mastai, Y. Cryst. Growth Des. 2008, 8, 3646.

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