Publications by authors named "Changhong Ke"

31 Publications

TRAIL-Armed ER Nanosomes Induce Drastically Enhanced Apoptosis in Resistant Tumor in Combination with the Antagonist of IAPs (AZD5582).

Adv Healthc Mater 2021 06 8;10(11):e2100030. Epub 2021 May 8.

School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, 51006, China.

Although mesenchymal stem cells (MSCs) can be engineered to deliver the TNF-related apoptosis-inducing ligand (TRAIL) as an effective anticancer therapy, the clinical application is hampered by the costly manufacturing of therapeutic MSCs. Therefore, it is needed to find an alternative cell-free therapy. In this study, TRAIL-armed endoplasmic reticulum (ER)-derived nanosomes (ERN-T) are successfully prepared with an average size of 70.6 nm in diameter from TRAIL transduced MSCs. It is demonstrated that the ERN-T is significantly more efficient for cancer cell killing than the soluble recombinant TRAIL (rTRAIL). AZD5582 is an antagonist of the inhibitors of apoptosis proteins (IAPs), and its combination with ERN-T induces strikingly enhanced apoptosis in cancerous but not normal cells. AZD5582 sensitizes resistant cancer cells to TRAIL through concomitant downregulation of IAP members like XIAP and the Bcl2 family member Mcl-1. Intravenously infused ERN-Ts accumulate in tumors for over 48 h indicating good tumor tropism and retention. The combination of ERN-T and AZD5582 drastically promotes therapeutic efficacy comparing with the cotreatment by rTRAIL and AZD5582 in a subcutaneous MDA-MB-231 xenograft tumor model. The data thus demonstrate that ERN-T can be a novel cell-free alternative to TRAIL-expressing MSC-based anticancer therapy and its efficacy can be drastically enhanced through combination with AZD5582.
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http://dx.doi.org/10.1002/adhm.202100030DOI Listing
June 2021

Ginsenoside Rb1 protected PC12 cells from Aβ-induced cytotoxicity via PPARγ activation and cholesterol reduction.

Eur J Pharmacol 2021 Feb 25;893:173835. Epub 2020 Dec 25.

Department of Chemistry, Jinan University, Guangzhou, 510632, China. Electronic address:

Accumulating evidences suggest that amyloid β (Aβ)-peptide plays a key role in pathogenesis of Alzheimer's disease (AD) through aggregation and deposition into plaques in neuronal cells. Membrane components such as cholesterol and gangliosides not only enhance the production of amyloidogenic Aβ fragments, but also appear to strengthen Aβ-membrane interaction. Ginsenoside Rb1 (GRb1) is a major active component of Panax, which is widely used to improve learning and memory. In the present study, whether ginsenoside Rb1 could protect pheochromocytoma cells (PC12 cells) from Aβ-induced cytotoxicity including inhibiting cell growth, inducing apoptosis, producing reactive oxygen species (ROS), destroying the cytoskeleton and bringing about membrane toxicity was investigated. Our results indicated that ginsenoside Rb1 could serve as an agonist of peroxisom proliferator-activated receptor-γ (PPARγ) and reduce the level of cholesterol in AD model cells. Reduction of the Aβ-induced cytotoxicity by lowering cholesterol was evidenced by reduction of ROS production, lipid peroxidation, and protection of cytoskeleton and membrane surface rigidity. Most importantly, the viability of PC12 cells increased from 50.42 ± 5.51% for the AD group to 102.72 ± 4.34% for the 50 μM ginsenoside Rb1 group with cholesterol reduction. Our results suggested that ginsenoside Rb1 might function as an effective candidate to promote reverse cholesterol transport and lower ROS production, therefore providing a new insight into prevention and treatment of AD.
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http://dx.doi.org/10.1016/j.ejphar.2020.173835DOI Listing
February 2021

Extracellular Vesicle Delivery of TRAIL Eradicates Resistant Tumor Growth in Combination with CDK Inhibition by Dinaciclib.

Cancers (Basel) 2020 May 4;12(5). Epub 2020 May 4.

Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 51006, China.

Tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) is a promising anti-cancer agent that rapidly induces apoptosis in cancer cells. Unfortunately, the clinical application of recombinant TRAIL (rTRAIL) has been hampered by its common cancer resistance. Naturally TRAIL is delivered as a membrane-bound form by extracellular vesicles (EV-T) and is highly efficient for apoptosis induction. SCH727965 (dinaciclib), a potent cyclin-dependent kinase (CDK) inhibitor, was shown to synergize with other drugs to get better efficacy. However, it has never been investigated if dinaciclib coordinates with EV-T to enhance therapeutic results. This study explores the potential of combination therapy with EV-T and dinaciclib for cancer treatment. EV-T was successfully derived from human TRAIL transduced cells and shown to partially overcome resistance of A549 cells. Dinaciclib was shown to drastically enhance EV-T killing effects on cancer lines that express good levels of death receptor (DR) 5, which are associated with suppression of CDK1, CDK9 and anti-apoptotic proteins. Combination therapy with low doses of EV-T and dinaciclib induced strikingly enhanced apoptosis and led to complete regression in A549 tumors without any adverse side effects observed in a subcutaneous xenograft model. Tumor infiltration of mass NK cells and macrophages was also observed. These observations thus indicate that the combination of EV-T with dinaciclib is a potential novel therapy for highly effective and safe cancer treatment.
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http://dx.doi.org/10.3390/cancers12051157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281120PMC
May 2020

Direct nanomechanical measurements of boron nitride nanotube-ceramic interfaces.

Nanotechnology 2019 Jan 2;30(2):025706. Epub 2018 Nov 2.

Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY 13902, United States of America.

Boron nitride nanotubes (BNNTs) are a unique class of light and strong tubular nanostructure and are highly promising as reinforcing additives in ceramic materials. However, the mechanical strength of BNNT-ceramic interfaces remains largely unexplored. Here we report the first direct measurement of the interfacial strength by pulling out individual BNNTs from silica (silicon dioxide) matrices using in situ electron microscopy techniques. Our nanomechanical measurements show that the average interfacial shear stress reaches about 34.7 MPa, while density functional theory calculations reveal strong bonded interactions between BN and silica lattices with a binding energy of -6.98 eV nm. Despite this strong BNNT-silica binding, nanotube pull-out remains the dominant failure mode without noticeable silica matrix residues on the pulled-out tube surface. The fracture toughness of BNNT-silica ceramic matrix nanocomposite is evaluated based on the measured interfacial strength property, and substantial fracture toughness enhancements are demonstrated at small filler concentrations.
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http://dx.doi.org/10.1088/1361-6528/aae874DOI Listing
January 2019

Author Correction: Quantitative Characterization of Structural and Mechanical Properties of Boron Nitride Nanotubes in High Temperature Environments.

Sci Rep 2018 Mar 14;8(1):4769. Epub 2018 Mar 14.

Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, New York, 13902, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-23081-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852136PMC
March 2018

Quantitative Characterization of Structural and Mechanical Properties of Boron Nitride Nanotubes in High Temperature Environments.

Sci Rep 2017 09 12;7(1):11388. Epub 2017 Sep 12.

Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, New York, 13902, USA.

The structural stability and mechanical integrity of boron nitride nanotubes (BNNTs) in high temperature environments are of importance in pursuit of their applications that are involved with extreme thermal processing and/or working conditions, but remain not well understood. In this paper, we perform an extensive study of the impacts of high temperature exposure on the structural and mechanical properties of BNNTs with a full structural size spectrum from nano- to micro- to macro-scale by using a variety of in situ and ex situ material characterization techniques. Atomic force microscopy (AFM) and high resolution transmission electron microscopy measurements reveal that the structures of individual BNNTs can survive at up to 850 °C in air and capture the signs of their structural degradation at 900 °C or above. In situ Raman spectroscopy measurements reveal that the BN bonds in BNNT micro-fibrils undergo substantial softening at elevated temperatures of up to 900 °C. The AFM-based nanomechanical compression measurements demonstrate that the mechanical integrity of individual BNNTs remain intact after being thermally baked at up to 850 °C in air. The studies reveal that BNNTs are structurally and mechanically stable materials in high temperature environments, which enables their usages in high temperature applications.
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http://dx.doi.org/10.1038/s41598-017-11795-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595806PMC
September 2017

Synergistic anti-tumor therapy by a comb-like multifunctional antibody nanoarray with exceptionally potent activity.

Sci Rep 2015 Oct 28;5:15712. Epub 2015 Oct 28.

International Joint Cancer Institute, the Second Military Medical University, Shanghai 200433, China.

Simultaneously blocking multiple mediators offers new hope for the treatment of complex diseases. However, the curative potential of current combination therapy by chronological administration of separate monoclonal antibodies (mAbs) or multi-specific mAbs is still moderate due to inconvenient manipulation, low cooperative effectors, poor pharmacokinetics and insufficient tumor accumulation. Here, we describe a facile strategy that arms distinct mAbs with cooperative effectors onto a long chain to form a multicomponent comb-like nano mAb. Unlike dissociative parental mAbs, the multifunctional mAb nanoarray (PL-RB) constructed from type I/II anti-CD20 mAbs shows good pharmacokinetics. This PL-RB simultaneously targets distinct epitopes on a single antigen (Ag) and neighboring Ags on different lymphocytes. This unique intra- and intercellular Ag cross-linking endows the multifunctional mAb nanoarray with potent apoptosis activity. The exceptional apoptosis, complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) that are synchronously evoked by the nano PL-RB are further synergistically promoted via enhanced permeability and retention (EPR), which resulted in high intratumor accumulation and excellent anti-lymphoma efficiency.
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http://dx.doi.org/10.1038/srep15712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623742PMC
October 2015

Suppression of Rituximab-resistant B-cell lymphoma with a novel multi-component anti-CD20 mAb nanocluster.

Oncotarget 2015 Sep;6(27):24192-204

International Joint Cancer Institute, the Second Military Medical University, Shanghai, China.

Although the anti-CD20 antibody Rituximab has revolutionized the treatment of Non-Hodgkin Lymphoma (NHL), resistance to treatment still existed. Thus, strategies for suppressing Rituximab-resistant NHLs are urgently needed. Here, an anti-CD20 nanocluster (ACNC) is successfully constructed from its type I and type II mAb (Rituximab and 11B8). These distinct anti-CD20 mAbs are mass grafted to a short chain polymer (polyethylenimine). Compared with parental Rituximab and 11B8, the ACNC had a reduced "off-rate". Importantly, ACNC efficiently inhibited Rituximab-resistant lymphomas in both disseminated and localized human NHL xenograft models. Further results revealed that ACNC is significantly potent in inducing caspase-dependent apoptosis and lysosome-mediated programmed cell death (PCD). This may help explain why ACNC is effective in suppressing rituximab-resistant lymphoma while Rituximab and 11B8 are not. Additionally, ACNC experienced low clearance from peripheral blood and high intratumor accumulation. This improved pharmacokinetics is attributed to the antibody-antigen reaction (active targeting) and enhanced permeability and retention (ERP) effect (passive targeting). This study suggested that ACNC might be a promising therapeutic agent for treatment of rituximab-resistant lymphomas.
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http://dx.doi.org/10.18632/oncotarget.4206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695179PMC
September 2015

A redox-sensitive micelle-like nanoparticle self-assembled from amphiphilic adriamycin-human serum albumin conjugates for tumor targeted therapy.

Biomed Res Int 2015 13;2015:987404. Epub 2015 May 13.

International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, China.

The application of chemotherapeutic drug adriamycin (ADR) in cancer therapy is limited by its side effects like high toxicity and insolubility. Nanomedicine offers new hope for overcoming the shortcomings. But how to increase in vivo stability and to control intracellular drug release is a key issue for nano-based formulations. Herein, the hydrophobic ADR was successfully linked to the biocompatible human serum albumin (HSA) by disulfide bond 3-(2-pyridyldithio) propionyl hydrazide (PDPH), resulting in amphiphilic HSA-ADR. The novel ADR-HSA micellar NPs which were thus assembled exhibited a well-defined stable core shell structure with glutathione (GSH) sensitive linkers. The stable PDPH linkers at extracellular level were broken by GSH at intracellular level with a controlled ADR release profile. The in vitro cytotoxicity against gastric cancer cells (NCI-N87) was obviously enhanced by such redox-sensitive ADR-HSA NPs. Additionally, as observed by IVIS Lumina II Imaging System (Xenogen), the intratumor accumulation of ADR-HSA NPs was much higher than that of HSA/ADR NPs due to its high stability. Consequently, the in vivo tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing gastric tumors. These in vitro/vivo results indicated that disulfide-bond-containing ADR-HSA NPs were an effective nanodrug delivery system for cancer therapy.
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http://dx.doi.org/10.1155/2015/987404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4444569PMC
March 2016

WITHDRAWN: Effective suppression of Rituximab-resistant B-cell lymphoma by a comb-like anti-CD20 mAb nanocluster.

Cancer Lett 2015 Feb 23. Epub 2015 Feb 23.

International Joint Cancer Institute, The Second Military Medical University, Shanghai, China. Electronic address:

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
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http://dx.doi.org/10.1016/j.canlet.2015.02.025DOI Listing
February 2015

Migration mechanism of mesenchymal stem cells studied by QD/NSOM.

Biochim Biophys Acta 2015 Mar 19;1848(3):859-68. Epub 2014 Dec 19.

Department of Chemistry, Jinan University, Guangzhou 510632, China.

The migration of mesenchymal stem cells (MSCs) plays a key role in tumor-targeted delivery vehicles and tumor-related stroma formation. However, there so far has been no report on the distribution of cell surface molecules during the VEGF-induced migration of MSCs. Here, we have utilized near-field scanning optical microscopy (NSOM) combined with fluorescent quantum dot (QD)-based nano-technology to capture the functional relationship between CD44 and CD29 adhesion molecules on MSCs and the effect of their spatial rearrangements. Before VEGF-induced migration of MSCs, both CD44 and CD29 formed 200-220 nm nano-domains respectively, with little co-localization between the two types of domains. Surprisingly, the size of the CD44 nano-domain rapidly increased in size to 295 nm and apparently larger aggregates were formed following MSC treatment with VEGF for 10 min, while the area of co-localization increased to 0.327 μm2. Compared with CD44, CD29 was activated obviously later, for the fact that CD29 aggregation didn't appear until 30 min after VEGF treatment. Consistently, its co-localization area increased to 0.917 μm2. The CD44 and CD29 nano-domains further aggregated into larger nano-domains or even formed micro-domains on the membrane of activated MSCs. The aggregation and co-localization of these molecules promoted FAK formation and cytoskeleton rearrangement. All of the above changes induced by VEGF contributed to MSC migration. Taken together, our data of NSOM-based dual color fluorescent imaging demonstrated for the first time that CD44, together with CD29, involved in VEGF-induced migration of MSCs through the interaction between CD44 and its co-receptor of VEGFR-2.
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http://dx.doi.org/10.1016/j.bbamem.2014.12.013DOI Listing
March 2015

Nano polymeric carrier fabrication technologies for advanced antitumor therapy.

Biomed Res Int 2013 4;2013:305089. Epub 2013 Dec 4.

International Joint Cancer Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China ; State Key Laboratory of Antibody Medicine and Targeting Therapy and Shanghai Key Laboratory of Cell Engineering, Shanghai 201203, China ; PLA General Hospital Cancer Center, PLA Graduate School of Medicine, Beijing 100853, China ; College of Pharmacy, Liaocheng University, 1 Hunan Road, Liaocheng, Shandong 25000, China ; Department of Chemistry, Jinan University, Guangzhou 510632, China.

Comparing with the traditional therapeutic methods, newly developed cancer therapy based on the nanoparticulates attracted extensively interest due to its unique advantages. However, there are still some drawbacks such as the unfavorable in vivo performance for nanomedicine and undesirable tumor escape from the immunotherapy. While as we know that the in vivo performance strongly depended on the nanocarrier structural properties, thus, the big gap between in vitro and in vivo can be overcome by nanocarrier's structural tailoring by fine chemical design and microstructural tuning. In addition, this fine nanocarrier's engineering can also provide practical solution to solve the problems in traditional cancer immunotherapy. In this paper, we review the latest development in nanomedicine, cancer therapy, and nanoimmunotherapy. We then give an explanation why fine nanocanrrie's engineering with special focus on the unique pathology of tumor microenvironments and properties of immunocells can obviously promote the in vivo performance and improve the therapeutic index of nanoimmunotherapy.
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http://dx.doi.org/10.1155/2013/305089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3867855PMC
July 2014

Nanomechanical cutting of boron nitride nanotubes by atomic force microscopy.

Nanotechnology 2013 Dec 27;24(50):505719. Epub 2013 Nov 27.

Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY 13902, USA.

The length of nanotubes is a critical structural parameter for the design and manufacture of nanotube-based material systems and devices. High-precision length control of nanotubes by means of mechanical cutting using a scriber has not materialized due to the lack of the knowledge of the appropriate cutting conditions and the tube failure mechanism. In this paper, we present a quantitative nanomechanical study of the cutting of individual boron nitride nanotubes (BNNTs) using atomic force microscopy (AFM) probes. In our nanotube cutting measurements, a nanotube standing still on a flat substrate was laterally scribed by an AFM tip. The tip-tube collision force deformed the tube, and eventually fractured the tube at the collision site by increasing the cutting load. The mechanical response of nanotubes during the tip-tube collision process and the roles of the scribing velocity and the frictional interaction on the tip-tube collision contact in cutting nanotubes were quantitatively investigated by cutting double-walled BNNTs of 2.26-4.28 nm in outer diameter. The fracture strength of BNNTs was also quantified based on the measured collision forces and their structural configurations using contact mechanics theories. Our analysis reports fracture strengths of 9.1-15.5 GPa for the tested BNNTs. The nanomechanical study presented in this paper demonstrates that the AFM-based nanomechanical cutting technique not only enables effective control of the length of nanotubes with high precision, but is also promising as a new nanomechanical testing technique for characterizing the mechanical properties of tubular nanostructures.
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http://dx.doi.org/10.1088/0957-4484/24/50/505719DOI Listing
December 2013

Direct measurements of the mechanical strength of carbon nanotube-poly(methyl methacrylate) interfaces.

Small 2013 Oct 18;9(19):3345-51. Epub 2013 Apr 18.

Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY, 13902, USA.

Understanding the interfacial stress transfer between carbon nanotubes (CNTs) and polymer matrices is of great importance to the development of CNT-reinforced polymer nanocomposites. In this paper, an experimental study is presented of the interfacial strength between individual double-walled CNTs and poly(methyl methacrylate) (PMMA) using an in situ nanomechanical single-tube pull-out testing scheme inside a high-resolution electron microscope. By pulling out individual tubes with different embedded lengths, this work reveals the shear lag effect on the nanotube-polymer interface and demonstrates that the effective interfacial load transfer occurs only within a certain embedded length. These results show that the CNT-PMMA interface possesses an interfacial fracture energy within 0.054-0.80 J/m(2) and a maximum interfacial strength within 85-372 MPa. This work is useful to better understand the local stress transfer on nanotube-polymer interfaces.
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http://dx.doi.org/10.1002/smll.201202771DOI Listing
October 2013

AFM studied the effect of celastrol on β1 integrin-mediated HUVEC adhesion and migration.

Scanning 2013 Sep-Oct;35(5):316-26. Epub 2012 Dec 12.

Department of Chemistry, College of Life Science and Technology, Jinan University, Guangzhou, China.

Integrin-mediated human umbilical vein endothelial cells (HUVECs) adhesion to the extracellular matrix plays a fundamental role in tumor-induced angiogenesis. Celastrol, a traditional Chinese medicine plant, has possessed anticancer and suppressed angiogenesis activities. Here, the mechanism underling the antiangiogenesis capacity of celastrol was investigated by exploring the effect of celastrol on β1(CD29) integrin-mediated cell adhesion and migration. Flow cytometry results showed that the HUVECs highly expressed CD29 and cell adhesion assay indicated that celastrol specifically inhibited the adhesion of HUVECs to fibronectin (FN) without affecting nonspecific adhesion to poly-L-lysine (PLL). After cell FN adhesion being inhibited, the cell surface nanoscale structure and adhesion force were detected by atomic force microscope (AFM). High-resolution imaging revealed that cell morphology and ultrastructure changed a lot after being treated with celastrol. The membrane average roughness (Ra) and the major forces were decreased from 31.34 ± 4.56 nm, 519.60 ± 82.86 pN of 0 μg/ml celastrol to 18.47 ± 6.53 nm, 417.79 ± 53.35 pN of 4.0 μg/ml celastrol, 10.54 ± 2.85 nm, 258.95 ± 38.98 pN of 8.0 μg/ml celastrol, respectively. Accompanying with the decrease of adhesion force, the actin cytoskeleton in the cells was obviously disturbed by the celastrol. All of these changes influenced the migration of HUVECs from the wound-healing migration assay. Taken together, our results suggest that celastrol can be as an inhibitor of HUVEC adhesion to FN. This work provides a novel approach to inhibition of tumor angiogenesis and tumor growth.
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http://dx.doi.org/10.1002/sca.21070DOI Listing
May 2014

Dielectrophoretic responses of DNA and fluorophore in physiological solution by impedimetric characterization.

Biosens Bioelectron 2013 Mar 28;41:649-55. Epub 2012 Sep 28.

Department of Electrical Engineering and Computer Science, the University of Tennessee, Knoxville, TN 37996, USA.

Characterization of the DNA's dielectrophoretic (DEP) behavior is the foundation of DNA manipulation by electric fields. This paper presents a label-free DNA differentiation technique by a combination of DEP response and impedimetric measurement on the microchip. In contrast to most of the recent studies on DEP manipulation of DNA that use deionized water or diluted DNA buffer where living biomolecules cannot survive, we used physiological solutions (PBS with 154 mM Na+) that are highly practical for pursuing DNA-based physical applications. The microchip, a commercial surface acoustic wave resonator, contains an array of interdigitated aluminum electrodes (1.4 μm width, 1.1 μm gap) on quartz substrate for DEP trap. Measurements were taken with a high precision impedance analyzer, which also acted as the excitation source to induce DEP response at 20 kHz, 50 kHz, 100 kHz, 300 kHz, 500 kHz, 1 MHz, 2 MHz and 5 MHz (N=3). To verify DEP response, fluorescence microscope images were captured before and after the electric excitation. Test results from the DEP experimentation after comparing with fluorescent images of pUC18 DNA show that a large change in impedance corresponds to positive DEP while little change corresponds to negative DEP. The strongest p-DEP and the maximum collection efficiency were observed around 300 kHz for supercoiled pUC18 and 100 kHz for linear λDNA. This work yields real-time impedimetric DEP response of DNA of different molecular conformations in practical settings. The technique can serve as the basis for submicron particle separation, disease diagnosis, cell life-circle research, and other applications in physiological surroundings.
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http://dx.doi.org/10.1016/j.bios.2012.09.036DOI Listing
March 2013

Radial elasticity of multi-walled boron nitride nanotubes.

Nanotechnology 2012 Mar 10;23(9):095703. Epub 2012 Feb 10.

Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY 13902, USA.

We investigated the radial mechanical properties of multi-walled boron nitride nanotubes (MW-BNNTs) using atomic force microscopy. The employed MW-BNNTs were synthesized using pressurized vapor/condenser (PVC) methods and were dispersed in aqueous solution using ultrasonication methods with the aid of ionic surfactants. Our nanomechanical measurements reveal the elastic deformational behaviors of individual BNNTs with two to four tube walls in their transverse directions. Their effective radial elastic moduli were obtained through interpreting their measured radial deformation profiles using Hertzian contact mechanics models. Our results capture the dependences of the effective radial moduli of MW-BNNTs on both the tube outer diameter and the number of tube layers. The effective radial moduli of double-walled BNNTs are found to be several-fold higher than those of single-walled BNNTs within the same diameter range. Our work contributes directly to a complete understanding of the fundamental structural and mechanical properties of BNNTs and the pursuits of their novel structural and electronics applications.
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http://dx.doi.org/10.1088/0957-4484/23/9/095703DOI Listing
March 2012

Engineering radial deformations in single-walled carbon and boron nitride nanotubes using ultrathin nanomembranes.

ACS Nano 2012 Feb 26;6(2):1814-22. Epub 2012 Jan 26.

Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, New York 13902, United States.

Radial deformations of carbon and boron-nitride nanotubes are of great importance to their respective electronic properties and applications. In this paper, we present a simple and practical approach of engineering radial deformations in single-walled carbon and boron-nitride nanotubes (SWCNTs and SW-BNNTs) through covering individual nanotubes lying on flat substrates with subnanometer-thick monolayer graphene oxide (GO) nanomembranes. The GO membrane conforms to and transversely compresses the underlying nanotube as a result of its adhesion binding interaction with the substrate. Our atomic force microscopy (AFM) imaging measurements reveal that the engineered net radial deformations of both types of tubes increase with the tube diameter and are more for SW-BNNTs compared with SWCNTs of the same tube diameter. Our results capture the net cross-section height reductions of up to 44.1% for SW-BNNTs and up to 29.7% for SWCNTs. Our work clearly demonstrates the effectiveness of our proposed approach for engineering and controlling the radial deformation in one-dimensional tubular nanostructures and opens a promising route for mechanical tuning of their electronic properties for novel nanoelectronics applications.
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http://dx.doi.org/10.1021/nn2048813DOI Listing
February 2012

Radial mechanical properties of single-walled boron nitride nanotubes.

Small 2012 Jan 14;8(1):116-21. Epub 2011 Nov 14.

Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY 13902, USA.

The radial mechanical properties of single-walled boron nitride nanotubes (SW-BNNTs) are investigated by atomic force microscopy. Nanomechanical measurements reveal the radial deformation of individual SW-BNNTs in both elastic and plastic regimes. The measured effective radial elastic moduli of SW-BNNTs are found to follow a decreasing trend with an increase in tube diameter, ranging from 40.78 to 1.85 GPa for tube diameters of 0.58 to 2.38 nm. The results show that SW-BNNTs have relatively lower effective radial elastic moduli than single-walled carbon nanotubes (SWCNTs). The axially strong, but radially supple characteristics suggest that SW-BNNTs may be superior to SWCNTs as reinforcing additives for nanocomposite applications.
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http://dx.doi.org/10.1002/smll.201100946DOI Listing
January 2012

Robust carbon-nanotube-based nano-electromechanical devices: understanding and eliminating prevalent failure modes using alternative electrode materials.

Small 2011 Jan;7(1):79-86

Dept. of Mechanical Engineering, Northwestern University, 2145 Sheridan Rd., Evanston, IL 60208-3111, USA.

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http://dx.doi.org/10.1002/smll.201001166DOI Listing
January 2011

Elastic deformation of carbon-nanotube nanorings.

Small 2010 Aug;6(15):1647-55

Department of Mechanical Engineering State University of New York at Binghamton Binghamton, NY 13902, USA.

A combined experimental-theoretical study of the mechanical deformation of carbon-nanotube (CNT) nanorings is presented. The CNT ring employed is formed by folding a long and thin single-walled-CNT bundle. The mechanical deformations of the CNT ring when it is pushed against and pulled away from a flat substrate are experimentally characterized in situ, inside a high-resolution scanning electron microscope through nanomanipulation. The experimental measurements clearly reveal that the CNT ring displays a purely elastic behavior during multiple repeated large-displacement deformation processes. A theoretical model based on nonlinear elastica theory is used to quantitatively study the mechanical behavior of the CNT ring and to interpret the experimental results. This work shows for the first time that van der Waals interactions between the CNT ring and the substrate have significant effects on the ring's elastic deformation, including a bifurcation in its force-displacement profile. The results suggest that CNT nanorings can be used as ultrasensitive force sensors and flexible and stretchable structural components in novel nanoscale mechanical and electromechanical systems.
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http://dx.doi.org/10.1002/smll.201000337DOI Listing
August 2010

Mechanical peeling of free-standing single-walled carbon-nanotube bundles.

Small 2010 Feb;6(3):438-45

Department of Mechanical Engineering, State University of New York at Binghamton, Binghamton, NY 13902, USA.

An in situ electron microscopy study is presented of adhesion interactions between single-walled carbon nanotubes (SWNTs) by mechanically peeling thin free-standing SWNT bundles using in situ nanomanipulation techniques inside a high-resolution scanning electron microscope. The in situ measurements clearly reveal the process of delaminating one SWNT bundle from its originally bound SWNT bundle in a controlled-displacement manner and capture the deformation curvature of the delaminated SWNT bundle during the peeling process. A theoretical model based on nonlinear elastica theory is employed to interpret the measured deformation curvatures of the SWNTs and to quantitatively evaluate the peeling force and the adhesion strength between bundled SWNTs. The estimated adhesion energy per unit length for each pair of neighboring tubes in the peeling interface based on our peeling experiments agrees reasonably well with the theoretical value. This in situ peeling technique provides a potential new method for separating bundled SWNTs without compromising their material properties. The combined peeling experiments and modeling presented in this paper will be very useful to the study of the adhesion interactions between SWNTs and their nonlinear mechanical behaviors in the large-displacement regime.
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http://dx.doi.org/10.1002/smll.200901807DOI Listing
February 2010

Detecting solvent-driven transitions of poly(A) to double-stranded conformations by atomic force microscopy.

Biophys J 2009 Apr;96(7):2918-25

Department of Mechanical Engineering and Materials Science, Center for Biologically Inspired Materials and Material Systems, Duke University, Durham, North Carolina, USA.

We report the results of direct measurements by atomic force microscopy of solvent-driven structural transitions within polyadenylic acid (poly(A)). Both atomic force microscopy imaging and pulling measurements reveal complex strand arrangements within poly(A) induced by acidic pH conditions, with a clear fraction of double-stranded molecules that increases as pH decreases. Among these complex structures, force spectroscopy identified molecules that, upon stretching, displayed two distinct plateau features in the force-extension curves. These plateaus exhibit transition forces similar to those previously observed in native double-stranded DNA (dsDNA). However, the width of the first plateau in the force-extension curves of poly(A) varies significantly, and on average is shorter than the canonical 70% of initial length corresponding to the B-S transition of dsDNA. Also, similar to findings in dsDNA, stretching and relaxing elasticity profiles of dspoly(A) at forces below the mechanical melting transition overlap but reveal hysteresis when the molecules are stretched above the mechanical melting transition. These results strongly suggest that under acidic pH conditions, poly(A) can form duplexes that are mechanically stable. We hypothesize that under acidic conditions, similar structures may be formed by the cellular poly(A) tails on mRNA.
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http://dx.doi.org/10.1016/j.bpj.2008.12.3939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711269PMC
April 2009

UVA generates pyrimidine dimers in DNA directly.

Biophys J 2009 Feb;96(3):1151-8

Center for Biologically Inspired Materials and Material Systems, Duke University, Durham, North Carolina, USA.

There is increasing evidence that UVA radiation, which makes up approximately 95% of the solar UV light reaching the Earth's surface and is also commonly used for cosmetic purposes, is genotoxic. However, in contrast to UVC and UVB, the mechanisms by which UVA produces various DNA lesions are still unclear. In addition, the relative amounts of various types of UVA lesions and their mutagenic significance are also a subject of debate. Here, we exploit atomic force microscopy (AFM) imaging of individual DNA molecules, alone and in complexes with a suite of DNA repair enzymes and antibodies, to directly quantify UVA damage and reexamine its basic mechanisms at a single-molecule level. By combining the activity of endonuclease IV and T4 endonuclease V on highly purified and UVA-irradiated pUC18 plasmids, we show by direct AFM imaging that UVA produces a significant amount of abasic sites and cyclobutane pyrimidine dimers (CPDs). However, we find that only approximately 60% of the T4 endonuclease V-sensitive sites, which are commonly counted as CPDs, are true CPDs; the other 40% are abasic sites. Most importantly, our results obtained by AFM imaging of highly purified native and synthetic DNA using T4 endonuclease V, photolyase, and anti-CPD antibodies strongly suggest that CPDs are produced by UVA directly. Thus, our observations contradict the predominant view that as-yet-unidentified photosensitizers are required to transfer the energy of UVA to DNA to produce CPDs. Our results may help to resolve the long-standing controversy about the origin of UVA-produced CPDs in DNA.
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http://dx.doi.org/10.1016/j.bpj.2008.10.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716568PMC
February 2009

Minimizing pulling geometry errors in atomic force microscope single molecule force spectroscopy.

Biophys J 2008 Oct 18;95(8):3991-8. Epub 2008 Jul 18.

Department of Mechanical Engineering and Materials Science, Center for Biologically Inspired Materials and Materials Systems, Pratt School of Engineering, Duke University, Durham, North Carolina 27708, USA.

In atomic force microscopy-based single molecule force spectroscopy (AFM-SMFS), it is assumed that the pulling angle is negligible and that the force applied to the molecule is equivalent to the force measured by the instrument. Recent studies, however, have indicated that the pulling geometry errors can drastically alter the measured force-extension relationship of molecules. Here we describe a software-based alignment method that repositions the cantilever such that it is located directly above the molecule's substrate attachment site. By aligning the applied force with the measurement axis, the molecule is no longer undergoing combined loading, and the full force can be measured by the cantilever. Simulations and experimental results verify the ability of the alignment program to minimize pulling geometry errors in AFM-SMFS studies.
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http://dx.doi.org/10.1529/biophysj.108.138842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2553119PMC
October 2008

Nanoscale detection of ionizing radiation damage to DNA by atomic force microscopy.

Small 2008 Feb;4(2):288-94

Center for Biologically Inspired Materials and Material Systems and Department of Mechanical, Engineering and Materials Science, Duke University, Durham, NC 27708, USA.

The detection and quantification of ionizing radiation damage to DNA at a single-molecule level by atomic force microscopy (AFM) is reported. The DNA damage-detection technique combining supercoiled plasmid relaxation assay with AFM imaging is a direct and quantitative approach to detect gamma-ray-induced single- and double-strand breaks in DNA, and its accuracy and reliability are validated through a comparison with traditional agarose gel electrophoresis. In addition, the dependence of radiation-induced single-strand breaks on plasmid size and concentration at a single-molecule level in a low-dose (1 Gy) and low-concentration range (0.01 ng microL(-1)-10 ng microL(-1)) is investigated using the AFM-based damage-detection assay. The results clearly show that the number of single-strand breaks per DNA molecule is linearly proportional to the plasmid size and inversely correlated to the DNA concentration. This assay can also efficiently detect DNA damage in highly dilute samples (0.01 ng microL(-1)), which is beyond the capability of traditional techniques. AFM imaging can uniquely supplement traditional techniques for sensitive measurements of damage to DNA by ionizing radiation.
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http://dx.doi.org/10.1002/smll.200700527DOI Listing
February 2008

Direct measurements of base stacking interactions in DNA by single-molecule atomic-force spectroscopy.

Phys Rev Lett 2007 Jul 5;99(1):018302. Epub 2007 Jul 5.

Department of Mechanical Engineering and Materials Science, Center for Biologically Inspired Materials and Material Systems, Duke University, Durham, North Carolina, USA.

We investigate the elasticity of two types of single-stranded synthetic DNA homopolydeoxynucletides, poly(dA) and poly(dT), by AFM-based single-molecule force spectroscopy. We find that poly(dT) exhibits the expected entropic elasticity behavior, while poly(dA) unexpectedly displays two overstretching transitions in the force-extension relationship. We suggest that these transitions, which occur at approximately 23 pN and approximately 113 pN, directly capture, for the first time, the mechanical signature of base-stacking interactions among adenines in DNA, in the absence of base pairing.
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http://dx.doi.org/10.1103/PhysRevLett.99.018302DOI Listing
July 2007

Detecting ultraviolet damage in single DNA molecules by atomic force microscopy.

Biophys J 2007 Sep 4;93(5):1758-67. Epub 2007 May 4.

Center for Biologically Inspired Materials and Material Systems and Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708, USA.

We report detection and quantification of ultraviolet (UV) damage in DNA at a single molecule level by atomic force microscopy (AFM). By combining the supercoiled plasmid relaxation assay with AFM imaging, we find that high doses of medium wave ultraviolet (UVB) and short wave ultraviolet (UVC) light not only produce cyclobutane pyrimidine dimers (CPDs) as reported but also cause significant DNA degradation. Specifically, 12.5 kJ/m(2) of UVC and 165 kJ/m(2) of UVB directly relax 95% and 78% of pUC18 supercoiled plasmids, respectively. We also use a novel combination of the supercoiled plasmid assay with T4 Endonuclease V treatment of irradiated plasmids and AFM imaging of their relaxation to detect damage caused by low UVB doses, which on average produced approximately 0.5 CPD per single plasmid. We find that at very low UVB doses, the relationship between the number of CPDs and UVB dose is almost linear, with 4.4 CPDs produced per Mbp per J/m(2) of UVB radiation. We verified these AFM results by agarose gel electrophoresis separation of UV-irradiated and T4 Endonuclease V treated plasmids. Our AFM and gel electrophoresis results are consistent with the previous result obtained using other traditional DNA damage detection methods. We also show that damage detection assay sensitivity increases with plasmid size. In addition, we used photolyase to mark the sites of UV lesions in supercoiled plasmids for detection and quantification by AFM, and these results were found to be consistent with the results obtained by the plasmid relaxation assay. Our results suggest that AFM can supplement traditional methods for high resolution measurements of UV damage to DNA.
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http://dx.doi.org/10.1529/biophysj.107.108209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1948057PMC
September 2007

Pulling geometry-induced errors in single molecule force spectroscopy measurements.

Biophys J 2007 May 26;92(9):L76-8. Epub 2007 Feb 26.

Department of Mechanical Engineering and Materials Science, Center For Biologically Inspired Materials and Material Systems, Pratt School of Engineering, Duke University, Durham, North Carolina, USA.

In AFM-based single molecule force spectroscopy, it is tacitly assumed that the pulling direction coincides with the end-to-end vector of the molecule fragment being stretched. By systematically varying the position of the attachment point on the substrate relative to the AFM tip, we investigate empirically and theoretically the effect of the pulling geometry on force-extension characteristics of double-stranded DNA. We find that increasing the pulling angle can significantly lower the force of the characteristic overstretching transition and increase the width of the plateau feature beyond the canonical 70%. These effects, when neglected, can adversely affect the interpretation of measured force-extension relationships. We quantitatively evaluate force and extension errors originating from this "pulling angle effect" and stress the need to correct the pulling geometry when stretching rigid molecules with an AFM.
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http://dx.doi.org/10.1529/biophysj.107.104901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1852342PMC
May 2007

Novel ultrananocrystalline diamond probes for high-resolution low-wear nanolithographic techniques.

Small 2005 Aug;1(8-9):866-74

Department of Mechanical Engineering, Northwestern University, Evanston, IL 60208, USA.

A hard, low-wear probe for contact-mode writing techniques, such as dip-pen nanolithography (DPN), was fabricated using ultrananocrystalline diamond (UNCD). Molding within anisotropically etched and oxidized pyramidal pits in silicon was used to obtain diamond tips with radii down to 30 nm through growth of UNCD films followed by selective etching of the silicon template substrate. The probes were monolithically integrated with diamond cantilevers and subsequently integrated into a chip body obtained by metal electroforming. The probes were characterized in terms of their mechanical properties, wear, and atomic force microscopy imaging capabilities. The developed probes performed exceptionally well in DPN molecular writing/imaging mode. Furthermore, the integration of UNCD films with appropriate substrates and the use of directed microfabrication techniques are particularly suitable for fabrication of one- and two-dimensional arrays of probes that can be used for massive parallel fabrication of nanostructures by the DPN method.
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http://dx.doi.org/10.1002/smll.200500028DOI Listing
August 2005