Giant Aggregates Research Articles

Inorganic salt-induced micellar morphologies in deep eutectic solvent: Structure and curcumin solubilization

Physico-spectroscopic data of deep eutectic solvent (DES, aquolines (choline chloride, ChCl: water (1:2 (DES I), 1:3 (DES II), 1:4 (DES III), and 1:5 (DES IV)) have been collected. The data differentiates DES I to DES III (DESs) from DES IV (molecular solution of ChCl). DESs (aquolines) are used to study association structures of surfactant + salt systems using spectrofluorometry, polarizing optical microscopy (POM), and dynamic light scattering (DLS). POM images show the formation of giant aggregates (vesicles, up to 3.3 µm) in DTAB – aquoline – salt system which was further confirmed using DLS. These systems show excessive solubility enhancement of the poorly water-soluble curcumin (CCM), a well-known natural drug and food ingredient. Solubility of CCM shows the following order: water < DES < DES + salt < DTAB-DESs < DTAB-salt-aquoline. CCM shows up to 250-fold solubility in DTAB-KNO3-DES I system compared to water. The work forging a new methodology of achieving giant amphiphilic aggregates and their application in improving the aqueous solubilities/extraction of hydrophobic materials.

Toxicity of the model protein 3×GFP arises from degradation overload, not from aggregate formation.

Although protein aggregation can cause cytotoxicity, such aggregates can also form to mitigate cytotoxicity from misfolded proteins, although the nature of these contrasting aggregates remains unclear. We previously found that overproduction (op) of a three green fluorescent protein-linked protein (3×GFP) induces giant aggregates and is detrimental to growth. Here, we investigated the mechanism of growth inhibition by 3×GFP-op using non-aggregative 3×MOX-op as a control in Saccharomyces cerevisiae. The 3×GFP aggregates were induced by misfolding, and 3×GFP-op had higher cytotoxicity than 3×MOX-op because it perturbed the ubiquitin-proteasome system. Static aggregates formed by 3×GFP-op dynamically trapped Hsp70 family proteins (Ssa1 and Ssa2 in yeast), causing the heat-shock response. Systematic analysis of mutants deficient in the protein quality control suggested that 3×GFP-op did not cause a critical Hsp70 depletion and aggregation functioned in the direction of mitigating toxicity. Artificial trapping of essential cell cycle regulators into 3×GFP aggregates caused abnormalities in the cell cycle. In conclusion, the formation of the giant 3×GFP aggregates itself is not cytotoxic, as it does not entrap and deplete essential proteins. Rather, it is productive, inducing the heat-shock response while preventing an overload to the degradation system.

Finite porous medium induced aggregation behavior of active dumbbells induced

Many active substances in nature are in complex environments, such as animal populations passing through the jungles, microorganisms migrating in the soil, and bacteria designed to sense the porous environment of tumors. The behavior of active substances in complex environments is a subject worth exploring, because they have great application significance in biophysics, medical engineering, and industrial fields. In this work, we use active dumbbells to represent bacteria and other active substances with shape anisotropy, and use molecular dynamics simulation to study their permeation behaviors in finite porous media. We find that under low temperature and appropriate activity, active dumbbells can aggregate inside and outside the medium and form four stable aggregation structures, they being hollow giant aggregation, hollow aggregation in medium, dense giant aggregation, and dense aggregation in medium. The aggregation is caused by the small space of the medium region, and the geometric trap is easily formed when the active dumbbells meet in the medium. Unlike motility-induced phase separation, the formation of such an aggregation relies on the assistance of obstacles. The persistence of directional motion determines the degree of aggregation of active dumbbells. There are significant differences among the four aggregation structures in density distribution, polar order parameter, and thermodynamic temperature inside and outside the medium. Under certain conditions, the disorder of medium arrangement can promote the aggregation behavior of active dumbbells, and the increase of lattice constant makes it easier for active dumbbells to form dense aggregation. Our research findings contribute to a more in-depth understanding of the life activities of active substances in complex environments, thus providing new ideas for designing microfluidic devices, drug delivery and other medical operations.

Self-Stabilized Giant Aggregates in Water from Room-Temperature Ionic Liquids with an Asymmetric Polar-Apolar-Polar Architecture.

We report the assembly of four imidazolium bromides, each of which bears a naphthyl on one side of the imidazolium cation and a branched alkyl chain on the other. This design creates a new type of amphiphilic ionic liquid with an apolar-polar-apolar structure and a low melting point (mp, <-20 °C), which has not been achieved by reported counterparts bearing linear alkyl chains. In solvent-free states, microphase segregation occurs where polar and apolar domains arrange bicontinuously as proved by molecular dynamics (MD) simulations. When dispersed in water, self-stabilized giant aggregates formed with ultrahigh colloidal stability (up to years). MD simulations provide clues of discrete bicontinuous phases within the giant aggregates. These newly discovered self-assemblies provide a heterogeneous reservoir that can accommodate guest molecules including the highly apolar fullerene C60, paving the way for a wide range of potential applications.

Organoboron-Functionalization Enables the Hierarchical Assembly of Giant Polyoxometalate Nanocapsules.

The aggregation of molecular metal oxides into larger superstructures can bridge the gap between molecular compounds and solid‐state materials. Here, we report that functionalization of polyoxotungstates with organo‐boron substituents leads to giant polyoxometalate‐based nanocapsules with dimensions of up to 4 nm. A “lock and key” mechanism enables the site‐specific anchoring of aromatic organo‐boronic acids to metal‐functionalized Dawson anions [M3P2W15O62]9− (M=TaV or NbV), resulting in unique nanocapsules containing up to twelve POM units. Experimental and theoretical studies provide initial insights into the role of the organo‐boron moieties and the metal‐functionalized POMs for the assembly of the giant aggregates. The study therefore lays the foundations for the design of organo‐POM‐based functional nanostructures.

Wax-Deficient &lt;i&gt;Arabidopsis&lt;/i&gt; Mutant &lt;i&gt;cer1-1&lt;/i&gt; Shows Abnormal Tapetosomes, Elaioplasts, and Pollen Coat

Normal maturation of the pollen coat is important for pollination in higher plants. The pollen coat contains abundant lipids and proteins, which are derived from tapetum cell-specific organelles, i.e., the tapetosome and elaioplast. The wax-deficient mutant eceriferum1 (cer1) shows a conditional male sterile phenotype. It is considered that this phenotype is caused by dysfunction of the pollen coat, although cer1 mutant pollen coats appear normal at a particular stage. In the present study, abnormalities in the tapetum cells and pollen coat of cer1-1 mutants were observed by scanning electron microscope and light microscopic analysis. To investigate the effect of wax composition changes on the structure of the pollen coat, tapetosome, and elaioplast in cer1-1 mutants, we observed the ultrastructure of the cer1-1 male gametophyte at various developmental stages. We observed abnormal giant aggregation of the lipids, which might be due to a fusion of the tapetosome and elaioplast in the early bicellular pollen stage tapetum cell. On the contrary, in wild-type plants, the fusion of the tapetosome and elaioplast occurred at the late bicellular pollen stage. In cer1-1, abnormalities in the tapetum cell and the pollen coat might occur because of the unusual timing of fusion of the tapetosome and the elaioplast. This is the first report showing the role of tapetum wax in the maturation of the tapetosome and elaioplast, which may affect pollen coat function.

Anti-ADAMTS5 monoclonal antibodies: implications for aggrecanase inhibition in osteoarthritis.

The extracellular matrix of articular cartilage is structurally specialized for efficient absorption of mechanical impact. In particular, giant aggregates of the large chondroitin sulfate proteoglycan, aggrecan, with the glycosaminoglycan, hyaluronan, allow cartilage to resist compressive load. Proteolysis of aggrecan by members of the proteinase family ADAMTS (A disintegrin-like and metalloproteinase domain with thrombospondin type 1 motif), was identified as an early step in the inexorable destruction of cartilage in osteoarthritis (OA). Of the investigated proteinases, ADAMTS5 has emerged as a principal mediator of aggrecan loss in OA, convincingly so in mouse models, and with high probability in humans. ADAMTS5 has a bipartite organization, comprising a proteinase domain and an ancillary domain containing exosites for interaction with aggrecan and other substrates. In a recent issue of this journal, Santamaria et al. characterized anti-ADAMTS5 monoclonal antibodies isolated from a phage display library. By blocking the catalytic site of the ADAMTS5 immunogen with a synthetic inhibitor, the authors of the paper biased selection of antibodies to the ancillary domain. This work, together with other antibodies targeting ADAMTS5, offers diverse, high-affinity and, as far as can be determined, selective aggrecanase inhibitors. Mapping of their epitopes provided novel insights into ADAMTS5 interactions with aggrecan. These monoclonal antibodies deserve continued investigation for potential arthritis therapy, although their successful use will require a comprehensive understanding of the physiological roles of ADAMTS5, and its regulation, intrinsic properties and intermolecular interactions.

Calorimetric and Light Scattering Investigations of the Transition from Spherical to Wormlike Micelles of C₁₄TAB Triggered by Salicylate.

Although wormlike micelles (WLM) were first described more than 30 years ago, many aspects of their formation process are still unclear. Herein, a systematic experimental investigation of the process for wormlike micelle (WLM) formation in mixtures of tetradecyltrimethylammonium bromide (C14TAB) and salicylate (2-hydroxybenzoate) was carried out. This system was used as a model to investigate the conditions for the formation of the giant aggregate. For comparison, the other two isomers of salicylate (3- and 4-hydroxybenzoate) were also investigated, once in these cases wormlike micelles are not formed. The studies were based on calorimetric titration, static light scattering, and rheological measurements. Enthalpy changes upon titration of C14TAB into 2-hydroxybenzoate solutions revealed a highly cooperative and exothermic process that was associated with micelle growth. The size of the aggregates, obtained by static light scattering measurements, confirms the shape transition. In addition, the correlation of these two sets of results with measurements of micelle charge surface indicates that this transition occurs around the point of charge neutralization.

Diarmed (adamantyl/alkyl) surfactants from nitrilotriacetic acid

The compounds presented here constitute a clear example of molecular biomimetics as their design is inspired on the structure and properties of natural phospholipids. Thus novel double-armed surfactants have been obtained in which nitrilotriacetic acid plays the role of glycerol in phospholipids. The hydrophobic arms are linked to the head group through amide bonds (which is also the case of sphingomyelin): (R1NHCOCH2)(R2NHCOCH2)NCH2CO2H (R1 being CH3(CH2)11, CH3(CH2)17, CH3(CH2)7CHCH(CH2)8, and adamantyl, and R2=adamantyl). The dependence of the surface tension with concentration shows the typical profile of surfactants since a breaking point, which corresponds to the critical aggregation concentration (cac), is observed in all cases. The cac of these diarmed derivatives are about 1–3 orders of magnitude lower than those of classical monoalkyl derivatives used as reference compounds. In contrast to conventional surfactants, reversed trends in cac values and molecular areas at the solution–air interface have been observed. This anomalous behavior is tied to the structure of the surfactants and suggests that long and flexible alkyl chains should self-coil previous to the aggregation or adsorption phenomena. Above cac all compounds form large aggregates, globular in shape, which tend to associate forming giant aggregates.

An Unprecedented Octadecanuclear Copper(II) Pyrazolate–Phosphonate Nanocage: Synthetic, Structural, Magnetic, and Mechanistic Study

A novel octadecanuclear copper pyrazolate-phosphonate nanocage with a bowl-shaped arrangement of the copper(II) centers in the asymmetric unit is reported. Characterization of intermediates in both solid and solution states aids to propose the mechanism of such a giant aggregation. Magnetic studies affirm the presence of antiferromagnetic interactions between the adjacent copper(II) centers. Extensive supramolecular interactions result in a framework structure.

Test of Hofmeister-like series of anionic headgroups: clouding and micellar growth

Phenomenon of clouding in charged micellar solutions is a fairly recent addition to conventional phenomenon shown by aqueous nonionic micelles. In this paper, we have tested a Hofmeister-like ordering of charged headgroups in the context of cloud point (CP) and micellar growth. For this purpose, we have used various combinations of surfactant (sodium dodecyl sulfate, SDS; sodium dodecylbenzene sulfonate, SDBS; sodium salts of α-sulfonato myristic acid methyl ester, MES; and α-sulfonato palmitic acid methyl ester, PES) and tetra-n-butylammonium bromide (TBAB). Different surfactant concentrations and TBAB concentrations are used and CP measurements have been performed. CP values were found in the order SDBS < SDS < PES < MES for the same concentration of surfactant and TBAB. This order has been discussed in the light of water affinities of interacting ionic species (i.e., surfactant headgroup and TBA+ counterion). The ordering was found similar for the case of micellar growth studied by dynamic light scattering (DLS). A bimodal distribution of aggregate size was found that transforms to giant aggregates at CP. The micelles of roughly 10-nm size convert to aggregates of 1 μm. The study has a few novelties: (1) headgroup dependence of CP, (2) micellar growth on heating, and (3) confirmation of Hofmeister-like series of headgroup.

Surfactant-Assisted Assembly of Fullerene (C60) Nanorods and Nanotubes Formed at a Liquid–Liquid Interface

Herein we report the surfactant-triggered assembly of fullerene (C60) into 3D flowerlike microcrystals at the liquid-liquid interface. C60 crystals were grown using a liquid-liquid interfacial precipitation (LLIP) method by layering surfactant solution in butanol with a saturated solution of C60 in benzene. In the LLIP method, it is suggested that the crystal formation mechanism is driven by supersaturation related to the low C60 solubility in alcohol. We found that the dimensions of the synthesized C60 flowers depend on the concentration and surfactant type. In the absence of surfactant (i.e., in the butanol/benzene system), 1D C60 nanowhiskers (nanorods) and C60 nanotubes (diameter 400 nm-2 μm and length 5-20 μm) are obtained. However, when surfactants are incorporated into the system flowerlike microcrystals consisting of C60 nanotubes are observed. For instance, crystals grown at the interface of a 0.01% diglycerol monolaurate (C12G2) nonionic surfactant in butanol with benzene lead to the formation of flower-shaped microcrystals of average sizes in the range of 10-35 μm. To the best of our knowledge, this is the first example of the surfactant-assisted assembly of C60 crystals. X-ray diffraction (XRD) and transmission electron microscopy (TEM) measurements have shown that fullerene flowers have a hexagonal structure with cell dimensions of a = 2.539 nm and c = 1.021 nm, which differ from that of pristine C60. Mixtures of flower-shaped C60 crystals and free-standing C60 nanotubes are found in the 0.1% C12G2/butanol system. However, clusters or giant aggregates of nanowhiskers lacking any specific shape are observed in the 1% C12G2/butanol system although these crystals exhibit hexagonal close-packed structures. Flower-shaped C60 microcrystals are also observed with anionic surfactants cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC). C60 flowers obtained from 0.01% CTAB and 0.01% CTAC also exhibit hexagonal structures with cell dimensions of a = 2.329 nm and c = 1.273 nm, a = 2.459 nm and c = 0.938 nm, respectively. Our C60 flowers exhibit intense photoluminescence (PL) and a blue-shifted PL intensity maximum compared to the same parameters for pristine C60, demonstrating the potential to control the optoelectronic properties of fullerene-based nanostructures.

Self-assembly of brush-like amphiphilic statistical polymers: the effect of salt stimulus on the molecular associative mode

The solution properties of amphiphilic statistical polymers, originating from the nanostructures of macromolecular assemblies, strongly depend on the associative behaviours of the polymers. In this paper, we report the effect of salt stimulus on the associative mode of the 2-(acrylamido)-2-methylpropanesulphonic acid–2-(acrylamido)-dodecane sulphonic acid brush-like amphiphilic statistical polymers, employing steady-state fluorescence, dynamic light scattering and transmission electron micrograph methods. It was found that the stimulus effects work more intensely for the polymers with less hydrophobic side chains. As the salt concentration increases, the salt valence state increases or the salt structure adds an organic group, the polymer molecules associate at a lower critical concentration. Meanwhile the molecules undergo an intramolecular associative mode in preference to an intermolecular associative mode, forming hundreds of times smaller unimers rather than giant multipolymer aggregates.

Morphologies near Cloud Point in Aqueous Ionic Surfactant: Scattering and NMR Studies

Clouding phenomenon in ionic surfactant solution is fairly a new addition to the conventional phenomenon observed with nonionic counterpart. Various scattering and spectroscopic techniques, dynamic light scattering (DLS), small angle neutron scattering (SANS), and nuclear magnetic resonance (NMR), have been used to draw information regarding the aggregate morphologies (formed by an ionic surfactant, tetra-n-butylammonium dodecylsulphate, TBADS) when the surfactant solution passes through the cloud point (CP). DLS measurements have shown that two morphologies are present when the system approaches the CP. The data revealed that individual micelles (~5 nm) convert to giant aggregates (~500 nm) over the range of temperature including the CP. SANS experiments have been performed to draw the information regarding individual micellar fraction below and above the CP. NMR spectra at different temperatures have been collected for TBADS solution. The broadening and the downfield shift of -N-CH(2) and -O-CH(2) proton peaks support the micellar growth as the sample was heated. The above peaks show splitting (into two each) confirming the presence of two morphologies around the CP. It is noted that conversion of only a small fraction of individual micelles is responsible for the clouding.

Morphological Analysis of 13 LMNA Variants Identified in a Cohort of 324 Unrelated Patients With Idiopathic or Familial Dilated Cardiomyopathy

Mutations in the LMNA gene, encoding lamins A/C, represent a significant cause of dilated cardiomyopathy. We recently identified 18 protein-altering LMNA variants in a cohort of 324 unrelated patients with dilated cardiomyopathy. However, at least one family member with dilated cardiomyopathy in each of 6 pedigrees lacked the LMNA mutation (nonsegregation), whereas small sizes of 5 additional families precluded definitive determinations of segregation, raising questions regarding contributions by those variants to disease. We have consequently expressed, in COS7 cells, GFP-prelamin A (GFPLaA) fusion constructs incorporating the 6 variants in pedigrees with nonsegregation (R101P, A318T, R388H, R399C, S437Hfsx1, and R654X), the 4 variants in pedigrees with unknown segregation (R89L, R166P [in 2 families], I210S, R471H), and 3 additional missense variants (R190Q, E203K, and L215P) that segregated with disease. Confocal immunofluorescence microscopy was used to characterize GFP-lamin A localization and nuclear morphology. Abnormal phenotypes were observed for 10 of 13 (77%) variants (R89L, R101P, R166P, R190Q, E203K, I210S, L215P, R388H, S437Hfsx1, and R654X), including 4 of 6 showing nonsegregation and 3 of 4 with uncertain segregation. All 7 variants affecting coil 1B and the lamin A-only mutation, R654X, exhibited membrane-bound GFP-lamin A aggregates and nuclear shape abnormalities. Unexpectedly, R388H largely restricted GFP-lamin A to the cytoplasm. Equally unexpected were unique streaked aggregates with S437Hfsx1 and giant aggregates with both S437Hfsx1 and R654X. This work expands the recognized spectrum of lamin A localization abnormalities in dilated cardiomyopathy. It also provides evidence supporting pathogenicity of 10 of 13 tested LMNA variants, including some with uncertain or nonsegregation.

Polymer induced structures in cetylpyridinium chloride–octanol micellar system

The effect of octanol on the interaction of polyethylene glycol (PEG) and cetylpyridinium chloride (CPC) were investigated by viscosity, conductivity, differential scanning calorimetry (DCS), polarizing microscopy, Fourier transform infrared spectroscopy (FTIR) and rheology analysis. The aggregation of polymer-surfactant micelles takes place at a surfactant concentration higher than the critical micelle concentration. The long chain aliphatic alcohol (n-octanol) induced rapid structural transformation in the mixed micellar system by unusual cooperative micellization. The rheological behavior of the viscoelastic system reveals the presence of giant aggregates in this system. The lyotropic nature of the giant aggregates was monitored by DSC and polarizing microscopic studies, and which was confirmed by cryo-TEM.

Femtosecond Solvation Dynamics in a Micron-Sized Aggregate of an Ionic Liquid and P123 Triblock Copolymer

Dynamic light scattering studies indicate that addition of a room temperature ionic liquid (RTIL, [pmim][Br]), to a triblock copolymer (P123) micelle leads to the formation of giant P123-RTIL clusters of size (diameter) 40 nm in 0.9 M and 3500 nm (3.5 microm) in 3 M RTIL. They are much larger than a P123 micelle ( approximately 18 nm) or [pmim][Br] (1.3 nm). Dynamics in different regions of the P123-RTIL aggregate is probed by variation of the excitation wavelength (lambda(ex)) using femtosecond up-conversion. For lambda(ex) = 375 nm, the nonpolar core of the P123-RTIL aggregate is preferentially excited while lambda(ex) = 435 nm selects the polar corona region. Solvation dynamics and anisotropy decay of coumarin 480 (C480) in a P123-RTIL giant aggregate are markedly different from those in either P123 micelle or those in an aqueous solution of the RTIL. For lambda(ex) = 405 nm in 5 wt % P123 and 0.9 M RTIL average rotational time, (<tau(rot)> = 1350 ps) of C480 is approximately 7 times longer than that (200 ps) in an aqueous solution of the RTIL in the absence of P123 and is shorter than that (3000 ps) in a P123 micelle. In 0.9 M RTIL and 5 wt % P123, solvation dynamics in the corona region (lambda(ex) = 435 nm, <tau(s)> = 75 ps) is approximately 25 times faster than that at the core region (at lambda(ex) = 375 nm, <tau(s)> = 1900 ps). The solvation dynamics in the core of the P123-RTIL aggregate is faster than that in P123 micelle (3550 ps in the core) and is much slower than that (130 ps) in an aqueous solution containing 0.9 M RTIL. In the 3.5 microm sized aggregate (3 M RTIL and P123), the solvation dynamics in the core (<tau(s)> = 500 ps) is approximately 4 times faster than that in 0.9 M RTIL.

Macrothrombocytopenia: Investigating the Ultrastructure of Platelets and Fibrin Networks Using Scanning and Transmission Electron Microscopy

Macrothrombocytopenia is a rare condition where large, circulating platelets ranging between ~5 and 20 μm are found (typically platelets size range from 1.5 to 2.5 μm). The condition is also characterized by the prevalence of decreased numbers of circulating platelets, bleeding, short circulating times in blood, as well as abnormal platelet destruction. The current research investigates the scanning electron microscopy (SEM) and transmission electron microscopy (TEM) of platelet aggregates and fibrin networks of a family diagnosed with macrothrombocytopenia. Although TEM analysis of macrothrombocytopenia is not novel, little is known regarding the SEM analysis of platelet aggregates and fibrin networks. Here the authors show that macrothrombocytopenia have two different variations of giant platelet aggregates: a bulbous, giant aggregate that is very similar to control aggregates, and a giant flattened aggregate, with a compressed outer rim and a centrally placed area that forms a bulbous pseudopodia-like core. TEM micrographs of controls showed that, as previously seen in the literature, an aggregate contains dense bodies and alpha granules that carry, among other compounds, fibrinogen. TEM micrographs of the individuals with macrothrombocytopenia revealed aggregates with large vacuoles and areas mostly devoid of dense bodies and alpha granules. An interesting observation was that, in the presence of added human thrombin (to initially form the clot), fibrin fiber networks, comparable to that of control fibrin networks, were formed. This might be of clinical interest in the treatment regime and should be investigated further.

Brush-Type Amphiphilic Diblock Copolymers from “Living”/Controlled Radical Polymerizations and Their Aggregation Behavior

Two brush-type amphiphilic diblock copolymers, poly(poly(ethylene glycol)methyl ether methacrylate-block-polystyrene) (P(PEGMA)-b-PS) and poly(glycidyl methacrylate)-block-poly(poly(ethylene glycol)methyl ether methacrylate) (P(GMA)-b-P(PEGMA)) were synthesized, respectively, via consecutive atom-transfer radical polymerizations (ATRPs) and reversible addition-fragmentation chain-transfer (RAFT) polymerizations. The diblock copolymers were characterized by gel permeation chromatography (GPC), (1)H nuclear magnetic resonance (NMR) spectroscopy, and FT-IR spectroscopy. The aggregation behavior of the two amphiphilic diblock copolymers in water was also studied. Scanning electron and transmission electron microscopic images revealed that spherical micelles (40-80 nm in diameter) from self-assembly of the P(PEGMA)-b-PS copolymers and wormlike micelles (60-120 nm in length and 20-30 nm in diameter) from self-assembly of the P(GMA)-b-P(PEGMA) copolymers were prevalent. The spherical P(PEGMA)-b-PS micelles could self-assemble gradually into giant aggregates of several micrometers in diameter.

Unreal City: Reflections on London and the Novel in the Twentieth Century

The immensity and complexity of London have rendered it literally ‘unknowable’. Teasing out what impact the city has had on the lives of its citizens, and how its people have shaped and moulded the city they live in, has proved resistant alike to the geographer's science and the historian's art. But it is perhaps in London's fictions that city and people come most alive. Here the forces generated by this giant aggregation of people, in a place with long traditions yet nervously alive to every tic of fashion, can be worked through in characters drawn from the novelist's experience and imagination. The London novel in the twentieth century exceeded in scope, diversity and courage (if not in grandeur and genius) the great tradition established from the 1830s on. This rich seam, both deep and wide, is celebrated here through fictions that explore the excitement and strain of arriving in London; the boozy promises of London's pubs and London's prostitutes; and that point where history confronts the Londoner and shapes her destiny. It is in these texts that we feel what it means to be a Londoner. Description from the publisher's website: http://hwj.oxfordjournals.org/cgi/content/abstract/56/1/1