Spontaneous Self-assembly Process Research Articles

Self-Assembly of Stimuli-Responsive Hydrogel Nanostructures by Peptide Amphiphiles via Molecular Dynamics Simulations

Peptide amphiphiles (PA), which have been known to self-assemble into nanostructures such as cylindrical nanofibers and spherical micelles in hydrogel, are of significant interest due to their potential applications in tissue engineering, biomedical imaging, and drug delivery. A representative PA molecule is comprised of a hydrophobic alkyl tail, a short peptide sequence for intermolecular hydrogen bonding, a group of charged amino acids for enhanced solubility, and a region for bioactive signals to be transduced via cells or proteins. Smart biomaterials that are self-assembled from such PA molecules are known to undergo morphological transitions in response to specific physiological stimuli. Using a novel coarse-grained peptide/polymer model, which has been validated by comparison of equilibrium conformations from atomistic simulations, we have performed large-scale molecular dynamics simulations to examine the whole spontaneous self-assembly process (1). Starting from random configurations, these simulations result in the formation of nanostructures of various sizes and shapes as a function of electrostatics and temperature. At optimal conditions, the self-assembly mechanism for the formation of cylindrical nanofibers is deciphered involving a series of steps: (1) PA molecules quickly undergo micellization whose driving force is the hydrophobic interactions between alkyl tails; (2) neighboring peptide residues within a micelle engage in a slow ordering process that leads to the formation of β-sheets exposing the hydrophobic core; (3) spherical micelles merge together through an end-to-end mechanism to form cylindrical nanofibers that exhibit high structural fidelity to the proposed structure based on experimental data. As the temperature and electrostatics vary, PA molecules undergo alternative kinetic mechanisms, resulting in the formation of a wide spectrum of nanostructures. A phase diagram in the electrostatics-temperature plane is constructed delineating regions of morphological transitions in response to external stimuli. (1) doi: 10.1002/adhm.201200400.

A Perspective on the Science of Clusters

In this article, the interdisciplinary science of clusters is discussed in general terms. Different types of clusters across vast scales of matter, energy, space, and time in the physical world are discussed. Specific examples of clusters in chemistry and physics are used to illustrate various principles or models of clustering processes of atoms and molecules as well as to demonstrate the exquisite beauty and pattern of clusters and the clustering phenomena so ubiquitous in nature. Nowadays, “designer clusters” can be made with tailorable properties and used as “building blocks” to form supermolecules, or to construct large cluster-based hierarchical materials with tunable properties, or to fabricate cluster-based devices with specific functions, etc., thereby providing a materials base for nanotechnology. Clustering is a spontaneous self-assembly process and the similarity across scales reflects the intrinsic self-organization and self-similarity principle of the physical world. Geometry and symmetry transcend all clustering processes, in ordered as well as in disordered systems.

The Role of Electrostatics and Temperature on Morphological Transitions of Hydrogel Nanostructures Self‐Assembled by Peptide Amphiphiles Via Molecular Dynamics Simulations

Smart biomaterials that are self-assembled from peptide amphiphiles (PA) are known to undergo morphological transitions in response to specific physiological stimuli. The design of such customizable hydrogels is of significant interest due to their potential applications in tissue engineering, biomedical imaging, and drug delivery. Using a novel coarse-grained peptide/polymer model, which has been validated by comparison of equilibrium conformations from atomistic simulations, large-scale molecular dynamics simulations are performed to examine the spontaneous self-assembly process. Starting from initial random configurations, these simulations result in the formation of nanostructures of various sizes and shapes as a function of the electrostatics and temperature. At optimal conditions, the self-assembly mechanism for the formation of cylindrical nanofibers is deciphered involving a series of steps: (1) PA molecules quickly undergo micellization whose driving force is the hydrophobic interactions between alkyl tails; (2) neighboring peptide residues within a micelle engage in a slow ordering process that leads to the formation of β-sheets exposing the hydrophobic core; (3) spherical micelles merge together through an end-to-end mechanism to form cylindrical nanofibers that exhibit high structural fidelity to the proposed structure based on experimental data. As the temperature and electrostatics vary, PA molecules undergo alternative kinetic mechanisms, resulting in the formation of a wide spectrum of nanostructures. A phase diagram in the electrostatics-temperature plane is constructed delineating regions of morphological transitions in response to external stimuli.

Early self-reproduction, the emergence of division mechanisms in protocells

Synthetic Biology approaches are proposing model systems and providing experimental evidences that life can arise as spontaneous chemical self-assembly process where the ability to reproduce itself is an essential feature of the living system. The appearance of early cells has required an amphiphilic membrane compartment to confine molecular information against diffusion, and the ability to self-replicate the boundary layer and the genetic information. The initial spontaneous self-replication mechanisms based on thermodynamic instability would have evolved in a prebiotic and later biological catalysis. Early studies demonstrate that fatty acids spontaneously assemble into bilayer membranes, building vesicles able to grow by incorporation of free lipid molecules and divide. Early replication mechanisms may have seen inorganic molecules playing a role as the first catalysts. The emergence of a short ribozyme or short catalytic peptide may have initiated the first prebiotic membrane lipid synthesis required for vesicle growth. The evolution of early catalysts towards the simplest translation machine to deliver proteins from RNA sequences was likely to give early birth to one single enzyme controlling protocell membrane division. The cell replication process assisted by complex enzymes for lipid synthesis is the result of evolved pathways in early cells. Evolution from organic molecules to protocells and early cells, thus from chemistry to biology, may have occurred in and out of the boundary layer. Here we review recent experimental work describing membrane and vesicle division mechanisms based on chemico-physical spontaneous processes, inorganic early catalysis and enzyme based mechanisms controlling early protocell division and finally the feedback from minimal genome studies.

Porous graphene frame supported silicon@graphitic carbon via in situ solid-state synthesis for high-performance lithium-ion anodes

The synthesis of graphene-based composite materials for Li-ion batteries using an in situ growing technique is first proposed in this work. Graphene frame supported silicon@graphitic carbon granules were obtained through a one-step solid-state reaction using iron phthalocyanine (FePc) and silicon nanoparticles (SiNPs) as the precursors. Nitrogen-doped graphene was grown in situ around the SiNPs by pyrolyzing and re-carbonizing FePc, and a cross-linked graphene frame network was gradually formed. Simultaneously, SiNPs were wrapped by a thin graphitic carbon layer, and the strong interconnections between the graphene, graphitic carbon and SiNPs led to a spontaneous self-assembly process, resulting in the formation of μm scale granules with available nanoporosities and irregular channels. The self-assembled granules with excellent electrical conductivity can effectively accommodate the volume change of the SiNPs during the repeating discharge–charge processes, therefore high capacity, long cycle life, high Coulombic efficiency and superb rate capability have been realized. The synthesis strategy is facile, safe, low-cost and can be easily industrialized, providing a broadly applicable route for the in situ synthesis of more functional graphene-based composite materials.

ChemInform Abstract: Metallatriangles and Metallasquares: The Diversity Behind Structurally Characterized Examples and the Crucial Role of Ligand Symmetry

AbstractReview: ca. 100 refs.

Solid-state capture and real-time analysis of individual T cell activation via self-assembly of binding multimeric proteins on functionalized materials surfaces

Polyfunctional T cell responses are increasingly underpinning new and improved vaccination regimens. Studies of the nature and extent of these T cell responses may be facilitated if specific T cell populations can be assessed from mixed populations by ligand-mediated capture in a solid-state assay format. Accordingly, we report here the development of a novel strategy for the solid-state capture and real-time activation analyses of individual cognate T cells which utilizes a spontaneous self-assembly process for generating multimers of biotinylated class I major histocompatibility-peptide complex (MHCp) directly on the solid-state assay surface while also ensuring stability by covalent interfacial binding. The capture surface was constructed by the fabrication of multilayer coatings onto standard slides. The first layer was a thin polymer coating with surface aldehyde groups, onto which streptavidin was covalently immobilized, followed by the docking of multimers of biotinylated MHCp or biotinylated anti-CD45.1 monoclonal antibody. The high binding strength at each step of this immobilization sequence aims to ensure that artefacts such as (partial) detachment, or displacement by proteins from solution, would not interfere with the intended biological assays. The multilayer coating steps were monitored by X-ray photoelectron spectroscopy; data indicated that the MHCp proteins self-assembled in a multimeric form onto the streptavidin surface. Immobilized multimeric MHCp demonstrated the capacity to bind and retain antigen-specific T cells from mixed populations of cells onto the solid carrier. Furthermore, real-time confocal microscopic detection and quantification of subsequent calcium flux using paired fluorescent ratiometric probes facilitated the analysis of individual T cell response profiles, as well as population analyses using a combination of individual T cell events.

Self‐Organized Graphene Patterns

A simple route for the fabrication of a highly ordered surface pattern consisting of reduced graphene oxide (RG-O) platelets is developed, in which RG-O platelets modified with poly(ionic liquid) (PIL) undergo a spontaneous self-assembly process as a result of the controlled solvent evaporation. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Metallatriangles and metallasquares: the diversity behind structurally characterized examples and the crucial role of ligand symmetry

Reports on spontaneous self-assembly processes between metal fragments and organic ligands frequently tend to ignore the fact that the product isolated and structurally characterized in most cases is only one out of a more or less large series of feasible ones. This is true even for rings containing as few as three or four metal ions. Here we shall review metallatriangles and metallasquares containing predominantly cis-square-planar metal entities and a range of bidentate bridging ligands. The most significant features contributing to the number of possible stereoisomers appear to be ligand symmetry and flexibility, viz. rotation of two halves of a ligand about a single bond, or rotation of the whole ligand about the metal-donor atom bonds. With low-symmetry bidentate ligands the number of isomers increases dramatically with ring size as a consequence of an increase in possible connectivity patterns, hence linkage isomers, and an increase in possible rotamer states of the bridging ligands. In this tutorial review it is demonstrated how complexity increases as the symmetry of the bridging ligands is lowered from D(∞h) and D(2h) to C(∞v), C(2v), C(2h) and C(s). Special attention will be paid to cyclic tri- and tetranuclear complexes of substituted pyrimidine ligands (C(2v) and C(s) symmetries) as well as the flexible 2,2'-bipyrazine, which can adopt states of either C(2v) or C(2h) symmetry. Uses of these complexes and ways to reduce the number of isomers will be pointed out.

Synthesis of Size-Tunable Anatase TiO2 Nanospindles and Their Assembly into Anatase@Titanium Oxynitride/Titanium Nitride−Graphene Nanocomposites for Rechargeable Lithium Ion Batteries with High Cycling Performance

This paper embarks upon three levels of undertaking ranging from nanomaterials synthesis to assembly and functionalization. First, we have prepared size-tunable anatase TiO(2) nanospindles via a hydrothermal process by using tubular titanates as self-sacrificing precursors. Second, we have densely dispersed the TiO(2) nanospindles onto functional graphene oxides (GO) via a spontaneous self-assembly process. After annealing of the TiO(2)/GO hybrid nanocomposite in an NH(3) gas flow, the TiO(2) surface was effectively nitridated and the GO was reduced to graphene sheets (GS) in order to further fortify the electronic functionality of the nanocomposite. Third, the anatase@oxynitride/titanium nitride-GS (TiO(2)@TiO(x)N(y)/TiN-GS) hybrid nanocomposite was studied as an anode material for lithium-ion batteries (LIBs), showing excellent rate capability and cycling performance compared to the pure TiO(2) nanospindles. Our systematic studies have revealed that the TiO(2)@TiO(x)N(y)/TiN-GS nanocomposites with graphene nanosheets covered with the TiO(2)@TiO(x)N(y)/TiN nanospindles on both sides provide a promising solution to the problems of poor electron transport and severe aggregation of TiO(2) nanoparticles by enhancing both electron transport through the conductive matrix and Li-ion accessibility to the active material from the liquid electrolyte. More generally, the size-tunable TiO(2) nanospindles with their unique (101) outer surface planes provide an archetype for the in depth investigation of their surface-specific and size-dependent physicochemical properties.

Direct observation of macropore self-formation in hierarchically structured metal oxides

The current work presents an unprecedented direct observation of macropore formation in the spontaneous self-assembly process to obtain hierarchical meso/macroporous metal oxides made possible with the help of an unusual titanium alkoxide.

A Comparative Study of Macroporous Metal Oxides Synthesized via a Unified Approach

A variety of macroporous metal oxides was synthesized via a spontaneous self-assembly process in aqueous solution starting from organic alkoxide precursors under a common set of conditions to prese...

Real‐Time Tracking of Superparamagnetic Nanoparticle Self‐Assembly

The spontaneous self-assembly process of superparamagnetic nanoparticles in a fast-drying colloidal drop is observed in real time. The grazing-incidence small-angle X-ray scattering (GISAXS) technique is employed for an in situ tracking of the reciprocal space, with a 3 ms delay time between subsequent frames delivered by a new generation of X-ray cameras. A focused synchrotron beam and sophisticated sample oscillations make it possible to relate the dynamic reciprocal to direct space features and to localize the self-assembly. In particular, no nanoparticle ordering is found inside the evaporating drop and near-surface region down to a drop thickness of 90 microm. Scanning through the shrinking drop-contact line indicates the start of self-assembly near the drop three-phase interface, in accord with theoretical predictions. The results obtained have direct implications for establishing the self-assembly process as a routine technological step in the preparation of new nanostructures.

Spontaneous self-assembly process for threadlike micelles

More than 100 micros dissipative particle dynamics simulations were carried out to investigate the spontaneous formation process of threadlike micelles from the random configuration for surfactant molecules. Stable spherical micelles were formed during the earlier stage. These spherical micelles fused to each other and grew into rodlike and threadlike micelles during the later stage. The length and radius of a micelle were estimated by tracing the backbone positions and the distance between the head group particles and the backbone of the micelles, respectively. The ratio of the largest to the smallest principal moments of inertia for each micelle was calculated as the micelle shape.

A Highly Ordered Material from Magnetically Aligned Peptide Amphiphile Nanofiber Assemblies

Materials that are built up out of molecular building blocks via a spontaneous hierarchical self-assembly process have intrigued scientists for many years. Nature provides, in this respect, beautiful examples, where, through extreme control over recognition and consequent directed self-assembly on a molecular level, discrete objects are constructed, such as the triple helical rods found in collagen, virus capsids, or the ribosome. Our present synthetic capabilities allow us to introduce many noncovalent interactions into molecules to construct supramolecular assemblies. Besides hydrogen bonding and ionic interactions, one of the main driving forces for self-assembly in an aqueous environment is hydrophobic forces. It is the subtle interplay and balance between all forces that enable a system to smoothly generate well-defined assemblies. In this respect, peptide amphiphiles have gained much interest as molecular building blocks for the development of new surfactants with unprecedented properties, leading to novel applications in the fields of materials and biomedical research. Peptide amphiphiles have been shown to provide a starting point for the generation of materials with a high degree of order on a nanoscopic level that imparts a functional scaffold that can be applied for, for example, biomineralization or cell proliferation. However, the designer process normally stops at the stage of spontaneous assembly, and macroscopic control over the organization of the assemblies is often not obtained. One of the methods to introduce this next level of organization is a further processing step of the supramolecular materials using external forces. There are many different external forces that can be applied. Traditionally, mechanical alignment and electric forces for orientation of materials have often been used. Another interesting, although less often used directional force, is a strong magnetic field. Magnetic alignment is an extremely versatile technique that exploits the anisotropy in diamagnetic susceptibility of assemblies of molecules. Such a procedure is very attractive as it is contact free, homogeneously effective over the whole sample, and can be used to produce structured thin films as well as bulk material. One of the drawbacks of the use of magnetic fields is that the aligning force is very small. The ability to align structures depends on the anisotropy of the diamagnetic susceptibility of the molecules and the strength of the applied magnetic field, which results in an energy difference DE between parallel and perpendicularly aligned molecules determined by using Equation 1

Pattern Formation during T-Cell Adhesion

T cells form intriguing patterns during adhesion to antigen-presenting cells. The patterns are composed of two types of domains, which either contain short TCR/MHCp receptor-ligand complexes or the longer LFA-1/ICAM-1 complexes. The final pattern consists of a central TCR/MHCp domain surrounded by a ring-shaped LFA-1/ICAM-1 domain, whereas the characteristic pattern formed at intermediate times is inverted with TCR/MHCp complexes at the periphery of the contact zone and LFA-1/ICAM-1 complexes in the center. Several mechanisms have been proposed to explain the T-cell pattern formation. Whereas biologists have emphasized the role of active cytoskeletal processes, previous theoretical studies suggest that the pattern evolution may be caused by spontaneous self-assembly processes alone. Some of these studies focus on circularly symmetric patterns and propose a pivot mechanism for the formation of the intermediate inverted pattern. Here, we present a statistical-mechanical model which includes thermal fluctuations and the full range of spatial patterns. We confirm the observation that the intermediate inverted pattern may be formed by spontaneous self-assembly. However, we find a different self-assembly mechanism in which numerous TCR/MHCp microdomains initially nucleate throughout the contact zone. The diffusion of free receptors and ligands into the contact zone subsequently leads to faster growth of peripheral TCR/MHCp microdomains and to a closed ring for sufficiently large TCR/MHCp concentrations. At smaller TCR/MHCp concentrations, we observe a second regime of pattern formation with characteristic multifocal intermediates, which resemble patterns observed during adhesion of immature T cells or thymozytes. In contrast to other theoretical models, we find that the final T-cell pattern with a central TCR/MHCp domain is only obtained in the presence of active cytoskeletal transport processes.

Self-assembly of a unique hexadecanuclear [4 x (2 x 2)]-Pb16 'grid of grids' type structure.

A new ligand containing a linear sequence of four-tridentate chelating subunits built around alkoxide and pyrimidine bridging groups undergoes a spontaneous self-assembly process with Pb(CF3SO3)2 to produce a unique hexadecanuclear [4 x (2 x 2)] 'grid of grids' type structure with external dimensions of 26 A.

Serendipity and Rational Design of One-Dimensional Doubly Stranded Chains with Nanometric Cavities Based on AgI Coordination Chemistry

Spontaneous and cooperative self-assembly processes allowed the preparation of two complexes {[AgL12][X]}n [X = CF3SO3, (3a); X = BF4, (3b)] in quantitative yields, identified as 1-D doubly stranded chains. The X-ray molecular structures of 3a,b are reported. Complexes 3a,b are isostructural and crystallize in the triclinic unit cell. The structures of 3a and 3b show the formation of a one-dimensional coordination polymer exhibiting as an outstanding feature the presence of infinite chained metallomacrocycles with nanometric cavities. Interestingly, NMR spectroscopy and electrospray mass spectrometry suggest that the identified elemental sub-unit [AgL12]+ is the key building block which self-assembles to provide the inorganic polymers 3a,b. The effect of weakly coordinating counteranions and the assembling ligand L1 on the supermolecule design are presented and discussed. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Synaptic pattern formation during cellular recognition.

Cell-cell recognition often requires the formation of a highly organized pattern of receptor proteins (a synapse) in the intercellular junction. Recent experiments [e.g., Monks, C. R. F., Freiberg, B. A., Kupfer, H., Sciaky, N. & Kupfer, A. (1998) Nature (London) 395, 82-86; Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M. & Dustin, M. L. (1999) Science 285, 221-227; and Davis, D. M., Chiu, I., Fassett, M., Cohen, G. B., Mandelboim, O. & Strominger, J. L. (1999) Proc. Natl. Acad. Sci. USA 96, 15062-15067] vividly demonstrate a complex evolution of cell shape and spatial receptor-ligand patterns (several microns in size) in the intercellular junction during immunological synapse formation. The current view is that this dynamic rearrangement of proteins into organized supramolecular activation clusters is driven primarily by active cytoskeletal processes [e.g., Dustin, M. L. & Cooper, J. A. (2000) Nat. Immunol. 1, 23-29; and Wulfing, C. & Davis, M. M. (1998) Science 282, 2266-2269]. Here, aided by a quantitative analysis of the relevant physico-chemical processes, we demonstrate that the essential characteristics of synaptic patterns observed in living cells can result from spontaneous self-assembly processes. Active cellular interventions are superimposed on these self-organizing tendencies and may also serve to regulate the spontaneous processes. We find that the protein binding/dissociation characteristics, protein mobilities, and membrane constraints measured in the cellular environment are delicately balanced such that the length and time scales of spontaneously evolving patterns are in near-quantitative agreement with observations for synapse formation between T cells and supported membranes [Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M. & Dustin, M. L. (1999) Science 285, 221-227]. The model we present provides a common way of analyzing immunological synapse formation in disparate systems (e.g., T cell/antigen-presenting cell junctions with different MHC-peptides, natural killer cells, etc.).

Dinuclear metal complexes of Cd(II), Zn(II) and Fe(II) with triple-helical structure and predetermined chirality

The complex formation of members of the so-called chiragen ligand family (stereoselective linked bis-[4,5]-pineno-2,2′-bipyridines) with Cd(II), Zn(II) and Fe(II) was investigated. Using spectrophotometric titrations and electrospray MS it was determined that the major species formed in solution are complexes with an M:L=2:3 stoichiometry. Based on circular dichroism (CD) and NMR measurements, a triple-helical structure with enantiomerically pure homochiral configuration at the metal centers is proposed for these dinuclear complexes. This is one of the first examples of a spontaneous self-assembly process leading to a dinuclear triple-helicate with pronouced preference for the formation of one of the possible stereoisomers.