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Featured researches published by Xiubo Zhao.


Biomacromolecules | 2010

Antibacterial Activities of Short Designer Peptides: a Link between Propensity for Nanostructuring and Capacity for Membrane Destabilization

Cuixia Chen; Fang Pan; Shengzhong Zhang; Jing Hu; Meiwen Cao; Jing Wang; Hai Xu; Xiubo Zhao; Jian R. Lu

Amphiphilic peptides A(3)K, A(6)K, and A(9)K displayed an increasing propensity for nanoaggregation with increasing the size of hydrophobic alanine moiety, and the size and shape of the aggregates showed a steady transition from loose peptide stacks formed by A(3)K, long nanofibers by A(6)K, to short and narrow nanorods by A(9)K. This size and shape transition was broadly consistent with the trend predicted from interfacial packing and curvature change if these peptide surfactants were treated as conventional surfactants. The antibacterial capacity, defined by the killing of percentage of bacteria in a given time and peptide concentration, showed a strong correlation to peptide hydrophobicity, evident from both microscopic and fluorescence imaging studies. For A(9)K, the power for membrane permeation and bacterial clustering intensified with peptide concentration and incubation time. These results thus depict a positive correlation between the propensity for self-assembly of the peptides, their membrane penetration power, and bactericidal capacity. Although the exposure of A(9)K to a preformed DPPC membrane bilayer showed little structural disturbance, the same treatment to the preformed DPPG membrane bilayer led to substantial disruption of model membrane structure, a trend entirely consistent with the high selectivity observed from membrane hemolytic studies.


Chemistry: A European Journal | 2011

Self-assembly of short peptide amphiphiles: the cooperative effect of hydrophobic interaction and hydrogen bonding.

Shuyi Han; Sasa Cao; Yuming Wang; Jiqian Wang; Daohong Xia; Hai Xu; Xiubo Zhao; Jian R. Lu

The interplay between hydrogen bonding, hydrophobic interaction and the molecular geometry of amino acid side-chains is crucial to the development of nanostructures of short peptide amphiphiles. An important step towards developing their practical use is to understand how different amino acid side-chains tune hydrophobic interaction and hydrogen bonding and how this process leads to the control of the size and shape of the nanostructures. In this study, we have designed and synthesized three sets of short amphiphilic peptides (I(3)K, LI(2)K and L(3)K; L(3)K, L(4)K and L(5)K; I(3)K, I(4)K and I(5)K) and investigated how I and L affected their self-assembly in aqueous solution. The results have demonstrated a strong tendency of I groups to promote the growth of β-sheet hydrogen bonding and the subsequent formation of nanofibrillar shapes. All I(m)K (m = 3-5) peptides assembled into nanofibers with consistent β-sheet conformation, whereas the nanofiber diameters decreased as m increased due to geometrical constraint in peptide chain packing. In contrast, L groups had a weak tendency to promote β-sheet structuring and their hydrophobicity became dominant and resulted in globular micelles in L(3)K assembly. However, increase in the number of hydrophobic sequences to L(5)K induced β-sheet conformation due to the cooperative hydrophobic effect and the consequent formation of long nanofibers. The assembly of L(4)K was, therefore, intermediate between L(3)K and L(5)K, similar to the case of LI(2)K within the set of L(3)K, LI(2)K and I(3)K, with a steady transition from the dominance of hydrophobic interaction to hydrogen bonding. Thus, changes in hydrophobic length and swapping of L and I can alter the size and shape of the self-assembled nanostructures from these simple peptide amphiphiles.


Langmuir | 2011

Self-assembly of short Aβ(16-22) peptides: Effect of terminal capping and the role of electrostatic interaction

Kai Tao; Jiqian Wang; Peng Zhou; Chengdong Wang; Hai Xu; Xiubo Zhao; Jian R. Lu

We report the characterization of self-assembly of two short β-amyloid (Aβ) peptides (16-22), KLVFFAE and Ac-KLVFFAE-NH2, focusing on examining the effect of terminal capping. At pH 2.0, TEM and AFM imaging revealed that the uncapped peptide self-assembled into long, straight, and unbranched nanofibrils with a diameter of 3.8 ± 1.0 nm while the capped one formed nanotapes with a width of 70.0 ± 25.0 nm. CD analysis indicated the formation of β-sheet structures in both aggregated systems, but the characteristic CD peaks were less intense and less red-shifted for the uncapped than the capped one, indicative of weaker hydrogen bonding and weaker π-π stacking. Fluorescence and rheological measurements also confirmed stronger intermolecular attraction associated with the capped nanotapes. At acidic pH 2, each uncapped KLVFFAE molecule carries two positive charges at the N-terminus, and the strong electrostatic repulsion favors interfacial curving and twisting within the β-sheet, causing weakening of hydrogen bonds and π-π stacking. In contrast, capping reduces the charge by half, and intermolecular electrostatic repulsion is drastically reduced. As a result, the lateral attraction of β-sheets favors stronger lamellar structuring, leading to the formation of rather flat nanotapes. Flat tapes with similar morphological structure were also formed by the capped peptide at pH 12.0 where the charge on the capping end was reversed. This study has thus demonstrated how self-assembled nanostructures of small peptides can be manipulated through simple molecular structure design and tuning of electrostatic interaction.


Langmuir | 2011

Interfacial Immobilization of Monoclonal Antibody and Detection of Human Prostate-Specific Antigen

Xiubo Zhao; Fang Pan; Ben Cowsill; Jian R. Lu; Luis Garcia-Gancedo; Andrew J. Flewitt; Gregory M. Ashley; Jikui Luo

Antibody orientation and its antigen binding efficiency at interface are of particular interest in many immunoassays and biosensor applications. In this paper, spectroscopic ellipsometry (SE), neutron reflection (NR), and dual polarization interferometry (DPI) have been used to investigate interfacial assembly of the antibody [mouse monoclonal anti-human prostate-specific antigen (anti-hPSA)] at the silicon oxide/water interface and subsequent antigen binding. It was found that the mass density of antibody adsorbed at the interface increased with solution concentration and adsorption time while the antigen binding efficiency showed a steady decline with increasing antibody amount at the interface over the concentration range studied. The amount of antigen bound to the interfacial immobilized antibody reached a maximum when the surface-adsorbed amount of antibody was around 1.5 mg/m(2). This phenomenon is well interpreted by the interfacial structural packing or crowding. NR revealed that the Y-shaped antibody laid flat on the interface at low surface mass density with a thickness around 40 Å, equivalent to the short axial length of the antibody molecule. The loose packing of the antibody within this range resulted in better antigen binding efficiency, while the subsequent increase of surface-adsorbed amount led to the crowding or overlapping of antibody fragments, hence reducing the antigen binding due to the steric hindrance. In situ studies of antigen binding by both NR and DPI demonstrated that the antigen inserted into the antibody layer rather than forming an additional layer on the top. Stability assaying revealed that the antibody immobilized at the silica surface remained stable and active over the monitoring period of 4 months. These results are useful in forming a general understanding of antibody interfacial behavior and particularly relevant to the control of their activity and stability in biosensor development.


PLOS ONE | 2012

Immobilization of Lipases on Alkyl Silane Modified Magnetic Nanoparticles: Effect of Alkyl Chain Length on Enzyme Activity

Jiqian Wang; Gang Meng; Kai Tao; Min Feng; Xiubo Zhao; Zhen Li; Hai Xu; Daohong Xia; Jian R. Lu

Background Biocatalytic processes often require a full recycling of biocatalysts to optimize economic benefits and minimize waste disposal. Immobilization of biocatalysts onto particulate carriers has been widely explored as an option to meet these requirements. However, surface properties often affect the amount of biocatalysts immobilized, their bioactivity and stability, hampering their wide applications. The aim of this work is to explore how immobilization of lipases onto magnetite nanoparticles affects their biocatalytic performance under carefully controlled surface modification. Methodology/Principal Findings Magnetite nanoparticles, prepared through a co-precipitation method, were coated with alkyl silanes of different alkyl chain lengths to modulate their surface hydrophobicity. Candida rugosa lipase was then directly immobilized onto the modified nanoparticles through hydrophobic interaction. Enzyme activity was assessed by catalytic hydrolysis of p-nitrophenyl acetate. The activity of immobilized lipases was found to increase with increasing chain length of the alkyl silane. Furthermore, the catalytic activities of lipases immobilized on trimethoxyl octadecyl silane (C18) modified Fe3O4 were a factor of 2 or more than the values reported from other surface immobilized systems. After 7 recycles, the activities of the lipases immobilized on C18 modified nanoparticles retained 65%, indicating significant enhancement of stability as well through hydrophobic interaction. Lipase immobilized magnetic nanoparticles facilitated easy separation and recycling with high activity retaining. Conclusions/Significance The activity of immobilized lipases increased with increasing alkyl chain length of the alkyl trimethoxy silanes used in the surface modification of magnetite nanoparticles. Lipase stability was also improved through hydrophobic interaction. Alkyl silane modified magnetite nanoparticles are thus highly attractive carriers for enzyme immobilization enabling efficient enzyme recovery and recycling.


PLOS ONE | 2009

Latherin: a surfactant protein of horse sweat and saliva.

Rhona E. McDonald; Rachel I. Fleming; John G. Beeley; Douglas L. Bovell; Jian R. Lu; Xiubo Zhao; Alan Cooper; Malcolm W. Kennedy

Horses are unusual in producing protein-rich sweat for thermoregulation, a major component of which is latherin, a highly surface-active, non-glycosylated protein. The amino acid sequence of latherin, determined from cDNA analysis, is highly conserved across four geographically dispersed equid species (horse, zebra, onager, ass), and is similar to a family of proteins only found previously in the oral cavity and associated tissues of mammals. Latherin produces a significant reduction in water surface tension at low concentrations (≤1 mg ml−1), and therefore probably acts as a wetting agent to facilitate evaporative cooling through a waterproofed pelt. Neutron reflection experiments indicate that this detergent-like activity is associated with the formation of a dense protein layer, about 10 Å thick, at the air-water interface. However, biophysical characterization (circular dichroism, differential scanning calorimetry) in solution shows that latherin behaves like a typical globular protein, although with unusual intrinsic fluorescence characteristics, suggesting that significant conformational change or unfolding of the protein is required for assembly of the air-water interfacial layer. RT-PCR screening revealed latherin transcripts in horse skin and salivary gland but in no other tissues. Recombinant latherin produced in bacteria was also found to be the target of IgE antibody from horse-allergic subjects. Equids therefore may have adapted an oral/salivary mucosal protein for two purposes peculiar to their lifestyle, namely their need for rapid and efficient heat dissipation and their specialisation for masticating and processing large quantities of dry food material.


PLOS ONE | 2009

Solution Behavior and Activity of a Halophilic Esterase under High Salt Concentration

Lang Rao; Xiubo Zhao; Fang Pan; Yin Li; Yanfen Xue; Yanhe Ma; Jian R. Lu

Background Halophiles are extremophiles that thrive in environments with very high concentrations of salt. Although the salt reliance and physiology of these extremophiles have been widely investigated, the molecular working mechanisms of their enzymes under salty conditions have been little explored. Methodology/Principal Findings A halophilic esterolytic enzyme LipC derived from archeaon Haloarcula marismortui was overexpressed from Escherichia coli BL21. The purified enzyme showed a range of hydrolytic activity towards the substrates of p-nitrophenyl esters with different alkyl chains (n = 2−16), with the highest activity being observed for p-nitrophenyl acetate, consistent with the basic character of an esterase. The optimal esterase activities were found to be at pH 9.5 and [NaCl] = 3.4 M or [KCl] = 3.0 M and at around 45°C. Interestingly, the hydrolysis activity showed a clear reversibility against changes in salt concentration. At the ambient temperature of 22°C, enzyme systems working under the optimal salt concentrations were very stable against time. Increase in temperature increased the activity but reduced its stability. Circular dichroism (CD), dynamic light scattering (DLS) and small angle neutron scattering (SANS) were deployed to determine the physical states of LipC in solution. As the salt concentration increased, DLS revealed substantial increase in aggregate sizes, but CD measurements revealed the maximal retention of the α-helical structure at the salt concentration matching the optimal activity. These observations were supported by SANS analysis that revealed the highest proportion of unimers and dimers around the optimal salt concentration, although the coexistent larger aggregates showed a trend of increasing size with salt concentration, consistent with the DLS data. Conclusions/Significance The solution α-helical structure and activity relation also matched the highest proportion of enzyme unimers and dimers. Given that all the solutions studied were structurally inhomogeneous, it is important for future work to understand how the LipCs solution aggregation affected its activity.


Biomacromolecules | 2011

Designed antimicrobial and antitumor peptides with high selectivity.

Jing Hu; Cuixia Chen; Shengzhong Zhang; Xichen Zhao; Hai Xu; Xiubo Zhao; Jian R. Lu

We report a new class of cationic amphiphilic peptides with short sequences, G(IIKK)(n)I-NH(2) (n = 1-4), that can kill Gram-positive and Gram-negative bacteria as effectively as several well-known antimicrobial peptides and antibiotics. In addition, some of these peptides possess potent antitumor activities against cancer cell lines. Moreover, their hemolytic activities against human red blood cells (hRBCs) remain remarkably low even at some 10-fold bactericidal minimum inhibitory concentrations (MICs). When bacteria or tumor cells are cocultured with NIH 3T3 fibroblast cells, G(IIKK)(3)I-NH(2) showed fast and strong selectivity against microbial or tumor cells, without any adverse effect on NIH 3T3 cells. The high selectivity and associated features are attributed to two design tactics: the use of Ile residues rather than Leu and the perturbation of the hydrophobic face of the helical structure with the insertion of a positively charged Lys residue. This class of simple peptides hence offers new opportunities in the development of cost-effective and highly selective antimicrobial and antitumor peptide-based treatments.


Biomaterials | 2012

Molecular mechanisms of antibacterial and antitumor actions of designed surfactant-like peptides

Cuixia Chen; Jing Hu; Shengzhong Zhang; Peng Zhou; Xichen Zhao; Hai Xu; Xiubo Zhao; Mohammed Yaseen; Jian R. Lu

Biomimicry of antimicrobial peptides secreted by innate immune systems represents a major strategy in developing novel antibacterial treatments. There are however emerging concerns over the possible compromise of host natural defenses by these biomimetic peptides due to their structural similarity. In our recent work we have extended the search by exploring the potential from unnatural synthetic antimicrobial peptides. Here we show that a series of surfactant-like peptides (A(m)K(n), m ≥ 3, n = 1, 2) can kill not only bacteria but also cancerous HeLa cells in similar manner. Under the same experimental conditions, however, these peptides showed little affinity to NIH 3T3 cells and human red blood cells (hRBCs), thus demonstrating high biocompatibility in selective responses to host mammalian cells and low hemolysis. A(9)K(1) was most effective in killing HeLa cells, a trend consistent with their bactericidal effects against Escherichia coli and Bacillus subtilis. Mechanistic investigations through combined studies of SEM and fluorescence assays revealed that the killing of bacteria and cancerous cells was caused by disrupting cell membranes, initiated by electrostatic interactions between cationic peptides and negatively charged cell membranes. In contrast, the absence of such interactions in the case of NIH 3T3 and hRBCs over the same peptide concentration range rendered low cytotoxicity. The most effective killing power of A(9)K(1) within this series benefited from the combined effects of several factors including modest micellar concentration and balanced amphiphilicity, consistent with its propensity of self-assembly and effective membrane lytic power.


Biomaterials | 2010

Surface structural conformations of fibrinogen polypeptides for improved biocompatibility.

Mohammed Yaseen; Xiubo Zhao; Amy Freund; Alexander M. Seifalian; Jian R. Lu

This work reports on how incorporation of silica nanocages into poly(urethane) copolymers (PU) affects conformational orientations of adsorbed fibrinogen and how different surfaces subsequently influenced HeLa cell attachment and proliferation. Incorporation of 2 wt% silica nanocages into poly(urethane) (PU4) substantially altered the surface topography of the films and some 50% of the surface was covered with the nanocages due to their preferential exposure. AFM studies revealed the deposition of a dense protein network on the soft polymeric domains of PU4 and much reduced fibrinogen adsorption on the hard nanocage domains. As on the bare SiO(2) control surface, fibrinogen molecules adsorbed on top of the hard nanocages mainly took the dominant trinodular structures in monomeric and dimeric forms. In addition, net positively charged long alpha chains were prone to being hidden beneath the D domains whilst gamma chains predominantly remained exposed. Dynamic interfacial adsorption as probed by spectroscopic ellipsometry revealed fast changes in interfacial conformation induced by electrostatic interactions between different segments of fibrinogen and the surface, consistent with the AFM imaging. On the PU surfaces without nanocage incorporation (PUA), however, adsorbed fibrinogen molecules formed beads-like chain networks, consistent with the structure featured on the soft PU4 domains, showing very different effects of surface chemical nature. Monoclonal antibodies specific to the alpha and gamma chains showed reduced alpha but increased gamma chain binding at the silicon oxide control and PU4 surfaces, whilst on the PUA, C18 and amine surfaces (organic surface controls) the opposite binding trend was detected with alpha chain binding dominant, showing different fibrinogen conformations. Cell attachment studies revealed differences in cell attachment and proliferation, consistent with the different polypeptide conformations on the two types of surfaces, showing a strong preference to the extent of exposure of gamma chains.

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Jian R. Lu

University of Manchester

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Fang Pan

University of Manchester

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Hai Xu

China University of Petroleum

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W. I. Milne

University of Cambridge

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Jiqian Wang

China University of Petroleum

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