Our understanding of the formation and growth of solids from solution has shaped science for centuries. The classical nucleation and crystal growth theories provided a foundational framework, despite their necessary simplifications. Recent nonclassical concepts have challenged this canon and refined the general models of the molecular and mesoscale processes underlying solid-state genesis. This shift of paradigms triggered novel terminology, often coined ad hoc to describe unexpected observations, but also created ambiguity across disciplinary boundaries. Here, we review current terminology, summarize the perceived classical canon, clarify ambiguous concepts, correct recurring misconceptions, and highlight terms that require further specification. We draw connections between colloidal, molecular, and mineral systems to develop generalizing concepts, while emphasizing where analogous phenomenology arises from distinct mechanistic or stabilizing conditions. We further identify the Szilard postulate-that crystallization proceeds by addition of individual ions or molecules-as a key criterion for distinguishing classical from nonclassical nucleation and growth mechanisms. By clarifying terminology and conceptual boundaries, this review provides a reference framework and a field guide for current debates on classical and nonclassical nucleation and crystallization.

Amorphous calcium carbonate (ACC) is a central precursor in biomineralization, paleoclimate archives, and functional carbonate materials. Yet, how foreign ions regulate ACC nucleation and composition remains unclear. Here, we show that Mg-2(+), Sr-2(+), and Ba-2(+) modulate ACC formation through ion-specific mechanisms that defy simple solubility and classical nucleation arguments. All three ions incorporate into supra-ionic coordination clusters that act as compositional gatekeepers from which ACC forms by aggregation. Integration of Ba into clusters stabilizes the solution entropically, leading to progressive nucleation inhibition with increasing Ba/Ca ratios- counterintuitive, given the lower solubility of Ba- vs. Ca-carbonate. Sr exhibits retrograde behavior, inhibiting nucleation at low Sr/Ca ratios but promoting it at higher ratios. Mg is distinct: Mg shows formation of two cluster populations, and ACC nucleation proceeds presumably mainly from Mg-depleted clusters. Mg acts hereby as a two-stage regulator, first delaying nucleation through cluster integration and subsequently being expelled from clusters during cluster phase separation. Together, these findings reveal a spectrum of ion-specific nucleation interferences that challenge classical nucleation concepts: entropic nucleation inhibition (Ba), ratio-sensitive induction/inhibition (Sr), and nucleation-induced compositional change (Mg). Beyond fundamental insight, they provide chemical levers to program nucleation pathways, tune material composition, and decode biomineralization control mechanisms.

Calcium carbonate formation in the oceans is a major component of the global carbon cycle. Yet, nucleation and crystallisation in ionically-complex seawater are not well understood. Here, we investigate CaCO3 nucleation and growth using potentiometric titration experiments in model solutions directly relevant to marine calcifying organisms. We develop a new framework for the conceptual interpretation of titration experiments, based on influx and outflux of ions in a dynamic system, and demonstrate the influence of the seawater major ions on CaCO3 nucleation and precipitation dynamics. Before nucleation, we find a significant underrepresentation of Ca2+CO32- interactions in state-of-the-art ion speciation models, suggesting strong ion association in solution, in seawater at conditions relevant to biomineralisation. After precipitation, structural, microscopic, and isotopic analyses indicate the presence of a nano-scale, disordered phase at precipitate surfaces, potentially contributing to crystal growth through particle attachment. The disordered phase forms at or in vicinity of crystal surfaces, and not as a distinct amorphous precursor in solution. Our findings show that ion association-driven processes during nucleation and crystal growth may be the usual case for inorganic aragonite formation in greatly supersaturated solutions, possibly implying this is the case for all or most (bio)carbonates, which is a significant conceptual shift for the understanding of carbonate formation in marine settings.

Additives have a multifaceted impact on nucleation and crystal growth mechanisms, which still require further charting. This contribution maps out the influence of a typical organic amino acid additive, L-phenylalanine, on the crystallization of a model amino acid, L-glutamic acid. The nucleation and growth processes are strongly modulated under the effect of this additive, which ultimately significantly influences polymorphic selection, phase transformation, shape, size, and size distribution of the crystalline products. A mixture of α-glu and β-glu nuclei is formed at low additive concentrations, while only α-glu nuclei are found at high additive concentrations. Thus, this additive molecule preferably induced α-glu conformation, thereby triggering the nucleation of α-glu instead of β-glu, which resulted in polymorphic selection of α-glu. Moreover, this additive favorably adsorbs on the facets of α-glu crystals, thereby inhibiting heterogeneous nucleation of β-glu, resulting in impeding a critical phase transformation pathway of α-glu to β-glu. This additive also remarkably impacted crystalline products’ shape, size, and size distribution.

Bicarbonate (HCO3−) and sodium (Na+)-containing solutions contain droplets of a separate, bicarbonate-rich liquid condensed phase (LCP) that have higher concentrations of HCO3− relative to the bulk solution in which they reside. The existence and composition of the LCP droplets has been investigated by nanoparticle tracking analysis, nuclear magnetic resonance spectroscopy, refractive index measurements and X-ray pair distribution function analysis. The bicarbonate-rich LCP species is a previously unaccounted-for, ionic phenomenon which occurs even in solutions with solely monovalent cations. Its existence requires re-evaluation of models used to describe and model aqueous solution physicochemistry, especially those used to describe and model carbonate mineral formation.

Creating a cellular model of Alzheimer's disease (AD) that accurately recapitulates disease pathology has been a longstanding challenge. Recent studies showed that human AD neural cells, integrated into three-dimensional (3D) hydrogel matrix, display key features of AD neuropathology. Like in the human brain, the extracellular matrix (ECM) plays a critical role in determining the rate of neuropathogenesis in hydrogel-based 3D cellular models. Aging, the greatest risk factor for AD, significantly alters brain ECM properties. Therefore, it is important to understand how age-associated changes in ECM affect accumulation of pathogenic molecules, neuroinflammation, and neurodegeneration in AD patients and in vitro models. In this review, mechanistic hypotheses is presented to address the impact of the ECM properties and their changes with aging on AD and AD-related dementias. Altered ECM characteristics in aged brains, including matrix stiffness, pore size, and composition, will contribute to disease pathogenesis by modulating the accumulation, propagation, and spreading of pathogenic molecules of AD. Emerging hydrogel-based disease models with differing ECM properties provide an exciting opportunity to study the impact of brain ECM aging on AD pathogenesis, providing novel mechanistic insights. Understanding the role of ECM aging in AD pathogenesis should also improve modeling AD in 3D hydrogel systems.

The precipitation of struvite, a magnesium ammonium phosphate hexahydrate (MgNH4PO4⋅6H2O) mineral, from wastewater is a promising method for recovering phosphorous. While this process is commonly used in engineered environments, our understanding of the underlying mechanisms responsible for the formation of struvite crystals remains limited. Specifically, indirect evidence suggests the involvement of an amorphous precursor and the occurrence of multi-step processes in struvite formation, which would indicate non-classical paths of nucleation and crystallization. In this study, we use synchrotron-based in situ X-ray scattering complemented by cryogenic transmission electron microscopy to obtain new insights from the earliest stages of struvite formation. The holistic scattering data captured the structure of an entire assembly in a time-resolved manner. The structural features comprise the aqueous medium, the growing struvite crystals, and any potential heterogeneities or complex entities. By analysing the scattering data, we found that the onset of crystallization causes a perturbation in the structure of the surrounding aqueous medium. This perturbation is characterized by the occurrence and evolution of Ornstein-Zernike fluctuations on a scale of about 1 nm, suggesting a non-classical nature of the system. We interpret this phenomenon as a liquid-liquid phase separation (LLPS), which gives rise to the formation of the amorphous precursor phase preceding actual crystal growth of struvite. Our microscopy results confirm that the formation of Mg-struvite includes a short-lived amorphous phase, lasting >10 seconds.

Additives have a multifaceted impact on nucleation and crystal growth mechanisms, which still require further charting. This contribution maps out the influence of a typical organic amino acid additive, l-phenylalanine, on the crystallization of a model amino acid, l-glutamic acid. The nucleation and growth processes are strongly modulated under the effect of this additive by altered product solubility, enthalpy, entropy, and Gibbs free energy, which, ultimately, significantly impacts phase transformation, phase composition, and particle shape, size, and size distribution of the crystalline products. A mixture of α-glu and β-glu nuclei is formed at low additive concentrations, while only α-glu nuclei are found at high additive concentrations. The interfacial tension of α-glu nuclei is lower than that of β-glu nuclei, and therefore, the nucleation rate of α-glu is faster than the one of β-glu. Simulation results indicate that this additive molecule primarily capture/associate with β-glu molecules that disrupt the ordered arrangement of β-glu, resulting in triggering the homogeneous nucleation of α-glu instead of β-glu. This additive favorably adsorbs on the facets of α-glu, thereby inhibiting heterogeneous nucleation of β-glu, resulting in impeding a critical phase transformation pathway of α-glu to β-glu. The crystal growth is also remarkably affected by this additive: i) instead of the familiar prism shape, a variety of altered shapes such as prism with truncations, pyramid-like, and blade-like bodies form are induced, and (ii) a strongly modulated size and size distribution is also found.

Spatial localizing of skeletal proteins in biogenic minerals remains a challenge in biomineralization research. To address this goal, we developed a novel in situ mapping technique based on molecular recognition measurements via atomic force microscopy (AFM), which requires three steps: (1) the development and purification of a polyclonal antibody elicited against the target protein, (2) its covalent coupling to a silicon nitride AFM tip ('functionalization'), and (3) scanning of an appropriately prepared biomineral surface. We applied this approach to a soluble shell protein - accripin11 - recently identified as a major component of the calcitic prisms of the fan mussel Pinna nobilis [1]. Multiple tests reveal that accripin11 is evenly distributed at the surface of the prisms and also present in the organic sheaths surrounding the calcitic prisms, indicating that this protein is both intra- and inter-crystalline. We observed that the adhesion force in transverse sections is about twice higher than in longitudinal sections, suggesting that accripin11 may exhibit preferred orientation in the biomineral. To our knowledge, this is the first time that a protein is localized by molecular recognition atomic force microscopy with antibody-functionalized tips in a biogenic mineral. The 'pros' and 'cons' of this methodology are discussed in comparison with more 'classical' approaches like immunogold. This technique, which leaves the surface to analyze clean, might prove useful for clinical tests on non-pathological (bone, teeth) or pathological (kidney stone) biomineralizations. Studies using implants with protein-doped calcium phosphate coating can also benefit from this technology. STATEMENT OF SIGNIFICANCE: Our paper deals with an unconventional technical approach for localizing proteins that are occluded in biominerals. This technique relies on the use of molecular recognition atomic force microscopy with antibody-functionalized tips. Although such approach has been employed in other system, this is the very first time that it is developed for biominerals. In comparison to more classical approaches (such as immunogold), AFM microscopy with antibody-functionalized tips allows higher magnification and keeps the scanned surface clean for other biophysical characterizations. Our method has a general scope as it can be applied in human health, for non-pathological (bone, teeth) and pathological (kidney stone) biomineralizations as well as for bone implants coated with protein-doped calcium phosphate.

Amorphes Kalziumcarbonat (ACC) ist ein wichtiger Vorläufer in der Biomineralisierung und von zentraler Bedeutung für die geologische und industrielle Kalzifizierung. Einige kleine organische Moleküle haben die Fähigkeit, die Bildung, Zusammensetzung und Stabilität von ACC stark zu beeinflussen. In ihrem Forschungsartikel (e202208475) entschlüsseln Asher Schmidt, Dirk Zahn, Stephan E. Wolf et al. die zugrundeliegenden molekularen Mechanismen, die sowohl die Pränukleation als auch die Zusammensetzung der Lösung regulieren. Amorphes Kalziumcarbonat (ACC) ist ein wichtiger Vorläufer in der Biomineralisierung und von zentraler Bedeutung für die geologische und industrielle Kalzifizierung. Einige kleine organische Moleküle haben die Fähigkeit, die Bildung, Zusammensetzung und Stabilität von ACC stark zu beeinflussen. In ihrem Forschungsartikel (e202208475) entschlüsseln Asher Schmidt, Dirk Zahn, Stephan E. Wolf et al. die zugrundeliegenden molekularen Mechanismen, die sowohl die Pränukleation als auch die Zusammensetzung der Lösung regulieren. Organische Halbleiter Photokatalyse Polymere Heterogene Katalyse

ABSTRACT: The mechanism of polymorph selection is still not fully understood in crystallization. This study demonstrates the impact of Taylor vortex flow on the crystallization and polymorph selection of Lglutamic acid as an organic model compound. Our results show that amorphous intermediates preceded the formation of a crystalline phase. The morphology of these amorphous precursors-ranging from spherical, oval, and ellipsoidal to irregular shapes-was governed by the velocity of the Taylor vortex flow. We attribute this observation to a transient liquidlike state of the amorphous precursor; simulations indeed corroborated this assumption as the morphology of droplets of a liquidlike precursor varies with the velocity of fluid motion accordingly. The phase selectivity depended on the intensity of the Taylor vortex flow. We found that the metastable alpha-form crystallized at low Taylor numbers, whereas the thermodynamically stable beta-form was obtained at high Taylor numbers, suggesting an impact of Taylor vortex flow on the amorphous-to-crystalline rearrangement of the intermediates. Moreover, a critical value of the Taylor number as Ta similar to 3636 was determined, which triggered the fast formation of the beta-polymorph. We assume that the high shear rate and mass transfer of Taylor vortex flow facilitate the phase transformation from the alpha- to the beta-polymorph.

Understanding the underlying processes of biomineralization is crucial to a range of disciplines allowing us to quantify the effects of climate change on marine organisms, decipher the details of paleoclimate records and advance the development of biomimetic materials. Many biological minerals form via intermediate amorphous phases, which are hard to characterize due to their transient nature and a lack of long-range order. Here, using Monte Carlo simulations constrained by X-ray and neutron scattering data together with model building, we demonstrate a method for determining the structure of these intermediates with a study of amorphous calcium carbonate (ACC) which is a precursor in the bio-formation of crystalline calcium carbonates. We find that ACC consists of highly ordered anhydrous nano-domains of approx. 2 nm that can be described as nanocrystalline. These nano-domains are held together by an interstitial net-like matrix of water molecules which generate, on the mesoscale, a heterogeneous and gel-like structure of ACC. We probed the structural stability and dynamics of our model on the nanosecond timescale by molecular dynamics simulations. These simulations revealed a gel-like and glassy nature of ACC due to the water molecules and carbonate ions in the interstitial matrix featuring pronounced orientational and translational flexibility. This allows for viscous mobility with diffusion constants four to five orders of magnitude lower than those observed in solutions. Small and ultra-small angle neutron scattering indicates a hierarchically-ordered organization of ACC across length scales that allow us, based on our nano-domain model, to build a comprehensive picture of ACC formation by cluster assembly from solution. This contribution provides a new atomic-scale understanding of ACC and provides a framework for the general exploration of biomineralization and biomimetic processes.

Correction for ‘Progressive changes in crystallographic textures of biominerals generate functionally graded ceramics’ by David Wallis et al. , Mater. Adv. , 2022, DOI: 10.1039/d1ma01031j.

Small-molecular-weight (MW) additives can strongly impact amorphous calcium carbonate (ACC), playing an elusive role in biogenic, geologic, and industrial calcification. Here, we present molecular mechanisms by which additives regulate stability and composition of both CaCO3 solutions and solid ACC. Potent antiscalants inhibit ACC precipitation by interacting with prenucleation clusters (PNC); they specifically trigger and integrate into PNCs or feed PNC growth. Only PNC-interacting additives are traceable in ACC, considerably stabilizing it against crystallization. The selective incorporation of potent additives in PNCs is a reliable chemical label that provides conclusive chemical evidence that ACC is a molecular precipitate derived PNCs. Our results reveal additive-cluster interactions beyond established mechanistic conceptions. They reassess the role of small-MW molecules in crystallization and biomineralization, while breaking grounds for new sustainable antiscalants.

Biominerals with gradually-changing crystallographic textures are an unrecognized class of elastically-graded materials that are intrinsically toughened by stress delocalisation.

Amorphous CaCO 3 (ACC) is a metastable phase that is involved as a precursor in many carbonate biominerals formed by marine organisms. As such, experimental investigation of the geochemical properties of ACC precipitated under conditions relevant to marine calcifying organisms is necessary in order to improve our understanding of biomineralisation (e.g., the origin of ‘vital effects’), and to provide a basis for the interpretation of stable isotope proxy data that is routinely applied in paleoclimate reconstruction. We present δ 18 O data of ACC and crystalline carbonate precipitated via titration experiments in artificial seawater (ASW), to assess the influence of mechanisms of nucleation and crystallisation. Under the solution conditions chosen here (pH ~9, DIC = ~20 mM, Mg/Ca = 0-5), the measured δ 18 O values of the precipitates implies that the dominant control of the isotope signal significantly differs for crystalline and amorphous carbonates. Relatively slow titration experiments that yield crystalline carbonates are controlled by kinetic isotope fractionation during crystal growth, as indicated by δ 18 O values lower than expected for equilibrated crystallisation. The δ 18 O values of rapidly precipitated ACC, however, are enriched in 18 O relative to the crystalline precipitates, resembling that calculated for HCO 3. This indicates

Bombyx mori silks possess great potential in textile industries due to the large‐scale green production. However, the demand for silks with functional as well as mechanical properties are continuously rising due to the emergence of other functional textiles. It remains a great challenge to functionalize natural silk and simultaneously improve its mechanical properties. Inspired by the relationship between natural core–sheath structure and mechanical properties of cocoon silk, the application of a thin reduced graphene oxide (rGO) layer coated B. mori silk (GS) is shown via hydrogen interfacial interaction. The resultant rGO‐coated silk exhibits a remarkable tensile strength of 1137.7 MPa and toughness of 304.5 MJ m −3 , which are 1.9 and 2.6 times higher than that of pure B. mori silk, respectively. Moreover, the GS shows a high electrical conductivity of 0.37 S m −1 with great thermal and deformation sensitivity. The bioinspired approach provides a universal and facile strategy for functionalizing natural fibers by applying rGO nanosheets surface coating.

Biominerals are bioinorganic solid-state materials generated by organisms under mildest and sustainable conditions. These biogenic materials serve the host organism for vital functions, having undergone more than half a billion years of evolutionary optimization for function, resilience, energy efficiency, and endurance. The research field of biomineralization is a highly interdisciplinary field, contributing to life sciences, Earth sciences, and materials sciences. On the molecular level, biomineralization turns into a chemical discipline, a new branch of bioinorganic chemistry. It is a major task of bioinorganic solid-state chemistry to provide answers to the fundamental question of how organisms can exert such an exceptional level of control over the formation of an inorganic solid-state and to exploit the newly identified synthesis concepts for novel and biomimetic materials and synthesis processes. Herein, we will explore this new branch of bioinorganic chemistry, which thrives alongside the well-established and flourishing branch of biocoordination chemistry. We will review pertinent examples of biomineralization and fathom how their analysis and our mimesis attempts were capable of transforming our current conceptional knowledge on the genesis of solid-state material from solution and led to new and nonclassical crystallization concepts.

Here, we approach the issue of ACC ultrastructure by applying a method for determining atomically resolved structures of amorphous materials using Monte Carlo simulations constrained by both X-ray and neutron scattering data. This structural analysis approach allows us to develop a detailed model for ACC at the atomic level. Our findings reveal that synthetic ACC, rapidly precipitated at high pH, consists of two-nanometer sized units containing a high degree of near range order similar to partially disordered nano-crystals. Small-angle scattering analyses show a multi-scale hierarchical organisation of the structure, supportive of a multi-step colloid self-assembly process. Computer simulations and high-resolution transmission electron microscopy show that the mesostructure of ACC resembles that of a glassy gel with crystalline material in domains. Our findings support the formation of ACC by a nanoparticle aggregation process that likely starts from prenucleation clusters in solution.