Accurate measurement of tip-sample contact size during nanoindentation of viscoelastic materials

Polypropylene (PP) and amorphous selenium (a-Se) were used as prototype materials at room temperature to explore the problems that may exist in the accurate measurement of the reduced modulus of viscoelastic materials using depth-sensing nanoindentation. As has been reported previously by others, we observed that a "nose" in the load - displacement curve may occur during unloading, indicating significant creep effects at the onset of unloading. To accurately measure the elastic modulus in viscoelastic materials like PP or a-Se, both the contact stiffness and the contact area at the onset of unloading must be determined accurately. The issue of removing the influence of creep on the measurement of the contact stiffness using the Oliver - Pharr method has been addressed in a previous paper by Feng and Ngan. In this work, the effect of creep on contact-depth measurement is considered. Removal of creep effects in both contact stiffness and contact-area measurement leads to satisfactory prediction of the reduced moduli in PP and a-Se.published_or_final_versio

Viscoelastic effects during unloading in depth-sensing indentation

With polypropylene as a prototype viscoelastic material at room temperature, it was found that a "nose" may appear in the unloading segment of the load-displacement curve during nanoindentation when the holding time at peak load is short and/or the unloading rate is small, and when the peak load is high enough. The load at which the nose appears was also found to decrease linearly with decreasing unloading rate. A linear viscoelasticity analysis was performed to interpret this effect. The analysis predicts a linear variation between the nose load and the unloading rate, and the slope of such a linear variation is also shown to be proportional to the viscosity parameter of the material. Thus, by measuring the slope of the nose-load versus unloading rate plot at a given temperature, the viscosity parameter of the specimen can be found. This is a new way of measuring the viscosity parameter of a material in addition to the existing method of force modulation and noting the frequency response of the displacement.published_or_final_versio

A rate-jump method for characterization of soft tissues using nanoindentation techniques

The biomechanical properties of soft tissues play an important role in their normal physiological and physical function, and may possibly relate to certain diseases. The advent of nanomechanical testing techniques, such as atomic force microscopy (AFM), nano-indentation and optical tweezers, enables the nano/micro-mechanical properties of soft tissues to be investigated, but in spite of the fact that biological tissues are highly viscoelastic, traditional elastic contact theory has been routinely used to analyze experimental data. In this article, a novel rate-jump protocol for treating viscoelasticity in nanomechanical data analysis is described. © 2012 The Royal Society of Chemistry.postprin

Probing neutrino and Higgs sectors in SU(2)1×SU(2)2×U(1)YSU(2)_1 \times SU(2)_2 \times U(1)_Y model with lepton-flavor non-universality

The neutrino and Higgs sectors in the \mbox{SU(2)}_1 \times \mbox{SU(2)}_2 \times \mbox{U(1)}_Y model with lepton-flavor non-universality are discussed. We show that active neutrinos can get Majorana masses from radiative corrections, after adding only new singly charged Higgs bosons. The mechanism for generation of neutrino masses is the same as in the Zee models. This also gives a hint to solving the dark matter problem based on similar ways discussed recently in many radiative neutrino mass models with dark matter. Except the active neutrinos, the appearance of singly charged Higgs bosons and dark matter does not affect significantly the physical spectrum of all particles in the original model. We indicate this point by investigating the Higgs sector in both cases before and after singly charged scalars are added into it. Many interesting properties of physical Higgs bosons, which were not shown previously, are explored. In particular, the mass matrices of charged and CP-odd Higgs fields are proportional to the coefficient of triple Higgs coupling $\mu$. The mass eigenstates and eigenvalues in the CP-even Higgs sector are also presented. All couplings of the SM-like Higgs boson to normal fermions and gauge bosons are different from the SM predictions by a factor $c_h$, which must satisfy the recent global fit of experimental data, namely $0.995<|c_h|<1$. We have analyzed a more general diagonalization of gauge boson mass matrices, then we show that the ratio of the tangents of the $W-W'$ and $Z-Z'$ mixing angles is exactly the cosine of the Weinberg angle, implying that number of parameters is reduced by 1. Signals of new physics from decays of new heavy fermions and Higgs bosons at LHC and constraints of their masses are also discussed.Comment: 40 pages, 1 figure; Journal vesio

The biomechanics of drug-treated leukemia cells investigated using optical tweezers

Leukemia is a very common cancer worldwide, and different drugs have been applied to treat the disease. However, the influence of the drugs on the biomechanical properties of leukemia cells, which are related to the risk of leukostasis, is still unknown. Moreover, accurate measurement of biomechanical properties of leukemia cells is still a challenging task because of their non-adherent nature and high sensitivity to the surrounding physiological conditions. In this study, a protocol to measure the biomechanical properties of leukemia cells by performing indentation tests using optical tweezers is proposed. The biomechanical properties of normal leukemia cells and cells treated with various cancer drugs, including phorbol 12-myristate 13-acetate (PMA), all-trans retinoic acid (ATRa), Cytoxan (CTX), and Dexamethasone (DEX), were measured. The adhesion between the cells and certain proteins existing in the extracellular matrix, i.e., fibronetin and collagen I, was also characterized with the help of a static adhesion assay. It was found that after treatment by ATRa, CTX, and DEX, the cells became softer, and the adhesion between the cells and the proteins became weaker. PMA treatment caused no change in the stiffness of the HL60 cells, but increased the stiffness of the K562 cells, and increased the cell–protein adhesion of both K562 cells and HL60 cells.postprin

An improved method for the measurement of mechanical properties of bone by nanoindentation

Nanoindentation is widely used to measure the mechanical properties of bio-tissues. However, viscoelastic effects during the nanoindentation are seldom considered rigorously, although they are in general very significant in bio-tissues. In this study, a recently developed method for correcting the viscoelastic effects during nanoindentation is applied to mice bone samples. This method is found to yield reliable elastic modulus and hardness results from forelimb and femur cortical bone samples of C57 BL/6N and ICR mice. The creep properties of the samples are also characterized by a novel procedure using nanoindentation. The measured mechanical properties correlate well with the calcium content of the bone samples. © 2007 Springer Science+Business Media, LLC.postprin

An alternative method for continuous property measurement during depth-sensing indentation

Based on the Oliver-Pharr framework, an iteration scheme is proposed to continuously evaluate the hardness during monotonic loading in nanoindentation. The new method was applied to measure the hardness of various crystalline materials including Al, Cu, Ni3Al(Cr,B) and MgO, where an obvious Indentation Size Effect (ISE) was observed. In a-Se and PP, no ISE was observed when using exponential loading schemes at constant strain rates. The new method therefore produced the correct ISE behaviours in various materials under different loading situations.postprin

Accurate measurement of stiffness of leukemia cells and leukocytes using an optical trap by rate-jump method

Accurate measurement of the elastic modulus of soft biological cells in the micro/nano scale range is still a challenging task. Tests involving constant-rate loading often yield results that are rate dependent, due to the viscous component of the deformation. In this work, a rate-jump indentation method was employed in an optical tweezers system to measure the stiffness of non-adherent blood cells, which are the softest types of cells. Compared to the traditional Hertzian method of indentation, the rate-jump method is found to be able to yield invariant elastic modulus from K562 myelogenous leukemia cells. The optical tweezers indentation method proposed can therefore serve as a standard protocol for obtaining the intrinsic elastic modulus of extremely soft cells, with applied forces in the pico-newton range. This method is also found to be effective in grading the stiffness values of myelogenous leukemia cell lines (K562 and HL60) and normal leukocytes, indicating that it can be used to identify normal cells from diseased counterparts without biochemical analysis.postprin

Reliable measurement of elastic modulus of cells by nanoindentation in an atomic force microscope

The elastic modulus of an oral cancer cell line UM1 is investigated by nanoindentation in an atomic force microscope with a flat-ended tip. The commonly used Hertzian method gives apparent elastic modulus which increases with the loading rate, indicating strong effects of viscoelasticity. On the contrary, a rate-jump method developed for viscoelastic materials gives elastic modulus values which are independent of the rate-jump magnitude. The results show that the rate-jump method can be used as a standard protocol for measuring elastic stiffness of living cells, since the measured values are intrinsic properties of the cells. © 2011 Elsevier Ltd.postprin

Kinase profiling of liposarcomas using RNAi and drug screening assays identified druggable targets.

BackgroundLiposarcoma, the most common soft tissue tumor, is understudied cancer, and limited progress has been made in the treatment of metastatic disease. The Achilles heel of cancer often is their kinases that are excellent therapeutic targets. However, very limited knowledge exists of therapeutic critical kinase targets in liposarcoma that could be potentially used in disease management.MethodsLarge RNAi and small-molecule tyrosine kinase inhibitor screens were performed against the proliferative capacity of liposarcoma cell lines of different subtypes. Each small molecule inhibitor was either FDA approved or in a clinical trial.ResultsScreening assays identified several previously unrecognized targets including PTK2 and KIT in liposarcoma. We also observed that ponatinib, multi-targeted tyrosine kinase inhibitor, was the most effective drug with anti-growth effects against all cell lines. In vitro assays showed that ponatinib inhibited the clonogenic proliferation of liposarcoma, and this anti-growth effect was associated with apoptosis and cell cycle arrest at the G0/G1 phase as well as a decrease in the KIT signaling pathway. In addition, ponatinib inhibited in vivo growth of liposarcoma in a xenograft model.ConclusionsTwo large-scale kinase screenings identified novel liposarcoma targets and a FDA-approved inhibitor, ponatinib with clear anti-liposarcoma activity highlighting its potential therapy for treatment of this deadly tumor