Application Of External Force Research Articles

Bio-inspired adhesive systems for next-generation green manufacturing

Inspired by the remarkable adhesion properties of gecko lizards, bio-inspired dry adhesives with smart adhesion properties have been developed in the last decade. Compared to earlier dry adhesives, the recently developed ones exhibit excellent adhesion strength, smart directional adhesion, and structural robustness. With these unique adhesion properties, bio-inspired dry adhesive pads have strong potential for use in precision industries such as semiconductor or display manufacturing. In this communication, we present a new manufacturing technology based on advanced dry adhesive systems that enable precise manipulation of large-area substrates over repeating cycles without any requirement for external force application. This new manufacturing technique is also highly accurate and environment-friendly, and thus has strong potential as a next-generation clean manufacturing technology.

Effect of external pulling forces on the length distribution of peptides

BackgroundThe distribution of the length of a polypeptide, or that of the distance between any two of its atoms, is an important property as it can be analytically or numerically estimated for a number of polymer models. Importantly, it is directly measurable through a number of different experimental techniques. Length distributions can be straightforwardly assessed from molecular dynamics simulation; however, true convergence through full accurate coverage of the length range is difficult to achieve. MethodsThe application of external constant force combined with the weighted-histogram analysis method (WHAM) is used to enhance sampling of unlikely ‘long’ or ‘short’ conformations and obtain the potential of mean force, while also collecting dynamic properties of the chain under variable tension. ResultsWe demonstrate the utility of constant force to enhance the sampling efficiency and obtain experimentally measurable quantities on a series of short peptides, including charge-rich sequences that are known to be highly helical but whose properties are distinct from those of helical peptides undergoing helix–coil transitions. ConclusionsForce-enhanced sampling enhances the range and accuracy of the length-based potential of mean force of the peptide, in particular those sequences that contain increased numbers of charged residues. General significanceThis approach allows users to simultaneously probe the force-dependent behaviour of peptides directly, enhance the range and accuracy of the length-based PMF of the peptide and also test the convergence of simulations by comparing the overlap of PMF profiles from different constant forces. This article is part of a special issue entitled Recent developments of molecular dynamics.

Tuning molecular excitation energy with external forces

Mechanical forces can be coupled to chemical reactions modifying their chemical reactivity and physical properties. Among the latter, optical properties, and more specifically radiative absorption, is sensitive to external forces due to the clear dependence between structure and excitation energy. Here we develop theoretical and computational tools aimed to guide molecular design of new or modified chromophores with a mechano-responsive excitation energy. In particular, we describe a methodology for determining the optimal external force (i.e. with lower possible magnitude) modifying the excitation energy of a molecular system. This optimal external force may serve as a guide to conveniently modify chemically the system in order to make feasible the exertion of such forces. Moreover, as force pairs are the easiest and more frequent kind of external forces acting over a molecular system, a protocol to determine the more efficient force pair modulating the excitation energy is proposed. Finally, these methods are tested with a chromophore, the semibullvalene molecule, finding the more efficient way to reduce its excitation energy with the application of simple external forces.

Toward an Optomechanical Control of Photoswitches by Tuning Their Spectroscopical Properties: Structural and Dynamical Insights into Azobenzene.

A new methodology to calculate efficiently the absorption spectrum of a single molecule when subjected to mechanical stress is presented. As example, the developed methodology was applied to cis- and trans-azobenzene, commonly used as photoswitch in a wide variety of applications. The results show that both (1)(n,π*) and (1)(π,π*) optical transitions can be efficiently modulated by applying an external force. A structural analysis was performed to evaluate the role of each internal coordinate in the excitation process, taking into account the application of external forces at different positions of azobenzene. Moreover, stress-strain curves were calculated in order to determine the maximum applicable forces within the elastic region, highlighting notable differences between the mechanical properties of cis- and trans-azobenzene conformers. The optomechanical work obtained by elongation and compression steps is calculated for a single azobenzene molecule and compared to available experimental data. Finally, the implications derived from the application of azobenzene as main chain component of a linear polymer acting as a photoinduced motor are discussed.

Prevalence of musculoskeletal pain in school going adolescents using school bags - A co-relational research

Children aged 12 – 18 years undergo rapid musculoskeletal development and an application of external forces (school bags) cause musculoskeletal disorders. The aim of this investigation was to assess the prevalence of neck, shoulder and back pain in the 1st term in school going adolescents using school bags. A co-relational research was conducted in Mangalore which included 580 students aged 13 -15 years. Their bag weight, body weight and height was measured and the subjects having pain either in the neck, shoulder or back were given McGill Melzack pain questionnaire to be filled. Descriptive analysis revealed that the percentage of bag weight on body weight ratio is more in females (mean ± SD 9.18 ± 3.71) compared to males (mean ± SD 8.88 ± 3.65). 6.03% of subjects carried bag weight weighing more than 15%, out of which 8.57% subjects complained of pain either in the neck, shoulder or back. The correlation between bag weight and pain was analysed using Karl Pearson’s correlation which is perfect positive (0.78). Analysis of correlation between BMI with percentage of bag weight in males (0.413) is more compared to females (0.086). The prevalence of adolescents having pain in the 1st term of school was 2.93% due to school bags. Hence, it is important to investigate further and take appropriate measures for adolescent problems with the use of school bags as it is a predictor for musculoskeletal disorder in adulthood.

The role of fine-needle aspiration cytology and ultrasound elastography in predicting malignancy in thyroid nodules

Background It is crucial to have a clear diagnostic approach to ensure patients presenting with thyroid nodules are managed appropriately. Fine-needle aspiration cytology (FNAC) is the best preoperative test used for differentiating malignant from benign nodules. Cytology has certain limitations that restrict its use as a single diagnostic test. Ultrasound elastography (USE) is a newly developed technique that uses ultrasound to provide an estimation of tissue stiffness under application of external force. The aim of this study was to assess whether USE improves the accuracy of FNAC in predicting malignancy in thyroid nodules. Patients and methods This prospective study included 96 patients with a solitary thyroid nodule or dominant nodule in the setting of multinodular goiter from January 2011 to July 2012. They were examined using USE at the Radiology Department, National cancer Institute, Cairo University. Tissue stiffness was scored from 1 (low stiffness over the entire nodule) to 5 (high stiffness over the entire nodule and surrounding tissue). All patients were referred for FNAC at the Cytology Unit, Pathology Department. Cytological specimens were evaluated blindly (without knowing the scores of USE) and classified according to the recent Bethesda classification. All the studied patients underwent surgery and were evaluated for the final histopathological diagnoses. Results On FNAC, 46 of 61 cases (75.4%) with a final histopathological diagnosis of benign nodule had a negative diagnosis, whereas 34 of 35 cases (97.1%) with a final histopathological diagnosis of carcinoma had a positive diagnosis (P Conclusion USE is a promising imaging technique that can assist in the differential diagnosis of thyroid nodules with higher sensitivity, specificity, PPV, NPV, and diagnostic accuracy compared with FNAC. Therefore, it may be useful to introduce it into the routine clinical practice in association with FNAC.

A mechanically tunable microfluidic cell-trapping device

Controlled manipulation, such as isolation, positioning, and trapping of cells, is important in basic biological research and clinical diagnostics. Micro/nanotechnologies have been enabling more effective and efficient cell trapping than possible with conventional platforms. Currently available micro/nanoscale methods for cell trapping, however, still lack flexibility in precisely controlling the number of trapped cells. We exploited the large compliance of elastomers to create an array of cell-trapping microstructures, whose dimensions can be mechanically modulated by inducing uniformly distributed strain via application of external force on the chip. The device consists of two elastomer polydimethylsiloxane (PDMS) sheets, one of which bears dam-like, cup-shaped geometries to physically capture cells. The mechanical modulation is used to tune the characteristics of cell trapping to capture a predetermined number of cells, from single cells to multiple cells. Thus, enhanced utility and flexibility for practical applications can be attained, as demonstrated by tunable trapping of MCF-7 cells, a human breast cancer cell line.

P 154. State dependent effects of transcranial alternating current stimulation of the motor system: What you think matters

Introduction Recent evidences suggested that imperceptible transcranial alternating current stimulation (tACS) resonates in a frequency-specific manner with the endogenous cortical oscillatory activity. Such a phenomenon causes behavioral consequences on perceptual, motor and cognitive tasks. In the motor system, 20 Hz tACS in beta range, coincident with the idling rhythm of the motor cortex at rest, increased corticospinal output. Objectives To assess how tACS modulates corticospinal excitability in a differential frequency dependent fashion during motor imagery and rest, we delivered transcranial oscillatory frequencies on the primary motor cortex ranging from theta to gamma band. Thus, we aimed to verify whether facilitatory tACS effects persisted during motor imagery, a cognitive task which desynchronizes the rolandic 20 Hz rhythm of quiescent motor areas, thereby becoming theoretically less susceptible to resonance effects of beta stimulation. Materials and methods Eighteen fully healthy right-handed volunteers (8 females, 10 males; mean age 32.2 ± 7.05 years) underwent fourteen different randomized conditions. Both for motor imagery and for resting condition, a “basal 1” session (without tACS), tACS on the left motor cortex at 5 Hz ( θ band), 10 Hz ( α band), 20 Hz ( β band), 40 Hz ( γ band), as well as 20 Hz on the right parietal cortex (as a control for unspecific effects on cortical excitability) and a “basal 2” session (again without tACS), were run. Each session of stimulation lasted 1.5–2 min. TMS was applied over the sponge electrode used for tACS overlying the left M1. Corticospinal excitability changes during stimulation at different frequencies were indexed by motor evoked potentials (MEPs) through navigated Transcranial Magnetic Stimulation (TMS) of the primary motor cortex. MEPs were recorded from the right First Dorsal Interosseus. For motor imagery tasks, subjects were requested to visually imagine a thumb-index finger pinch grip with their right hand. Each TMS pulse was delivered 1–2 s after the initiation of the motor imagery task as well as for rest condition. Results A General Estimation Equation (factors motor imagery and rest x frequency conditions) showed that the maximal increase of corticospinal excitability took place when tACS was applied at 5 Hz and an additional slighter effect of 10 Hz tACS with subjects engaged in a motor imagery task. On the other hand, tACS at 20 Hz confirmed the maximal increase of corticospinal excitability with subjects at rest. Conclusions On one hand results confirmed the frequency-dependence effects of tACS. On the other hand a state-dependent effect of tACS emerged. The MEPs increase in theta range stimulation during motor imagery may reflect reinforcement of working memory processes required to mentally elaborate and “execute” the task. We infer that tACS induces an entrainment effect by dragging the endogenous oscillatory activity to the one induced by stimulation. This indicates that human brain motor processes might be driven and promoted by application of external sinusoidal electrical forces. Download high-res image (87KB) Download full-size image

Orientational ordering of colloidal dispersions by application of time-dependent external forces

We discuss a method of organizing incoherent motion of a colloidal suspension to produce synchronized, coherent motion, extending the discussion of our recent Letter [Moths and Witten, Phys. Rev. Lett. 110, 028301 (2013)]. The method does not require interaction between the objects. Instead, the effect is controlled by the "twist matrix" which gives the angular velocity of an asymmetric object in a fluid resulting from a weak external force. We analyze the two types of forcing considered in the Letter: a force alternating between two directions and a continuously rotating force. For the alternating force, we justify the claim of the Letter that under appropriate forcing conditions, the orientational entropy of the objects decreases indefinitely with time, on average. We provide a bound on that rate in terms of the twist matrix. For the case of rotating force, we derive conditions for phased-locked motion of the objects to the force and prove that there is only one stable phase-locked orientation under these conditions. We find numerically that the fastest alignment typically occurs for tilt angles of order unity. We discuss how the alignment effect scales with the object size for external forcing caused by gravity or an electric field. Under practical forcing conditions we estimate that the alignment should persist despite rotational diffusion for objects larger than about 10 microns. Potential misalignment owing to hydrodynamic interaction of the objects is estimated to be negligible at volume fractions smaller than about 10(-4.5) (10(-3)) when the forcing is gravitational (electrophoretic).

Spontaneous tubulation of membranes and vesicles reveals membrane tension generated by spontaneous curvature

Recent experimental studies on supported lipid bilayers and giant vesicles have shown that uni-lamellar membrane systems can undergo spontaneous tubulation, i.e., can form membrane tubules or nanotubes without the application of external forces. In the case of supported lipid bilayers, the tube formation was induced by the adsorption of antimicrobial peptides. In the case of giant vesicles, spontaneous tubulation was observed after the polymer solution inside the vesicles underwent phase separation into two aqueous phases. Here, these processes are studied theoretically and shown to be driven by membrane tension generated by spontaneous curvature. The latter curvature is estimated for different types of adsorbing particles, such as ions, small molecules, and macromolecules, that differ in their size and in their adsorption kinetics. When the two sides of the membranes are exposed to two different concentrations of these particles, the membranes will acquire a spontaneous (or preferred) curvature. Particularly large spontaneous curvatures are induced by the adsorption of amphipathic peptides and BAR domain proteins. Another mechanism that induces spontaneous curvature is provided by different depletion layers in front of the two sides of the membranes. Irrespective of its molecular origin, a spontaneous curvature is predicted to generate a tension in weakly curved membranes, a 'spontaneous' tension that can vary over several orders of magnitudes and can be as high as 1 mJ m(-2). The concept of spontaneous tension is first used to explain the spontaneous tubulation of supported lipid bilayers when exposed to adsorbing particles. This tubulation process is energetically preferred when the spontaneous tension exceeds the adhesive strength of the underlying solid support. Furthermore, in the case of giant vesicles, the spontaneous tension can balance the osmotic pressure difference between the interior and exterior aqueous compartment. The vesicles are then able to form stable cylindrical nanotubes that protrude into the vesicle interior as observed recently for membranes in contact with two aqueous polymer phases. In these latter systems, the vesicle membranes are governed by two spontaneous tensions that can be directly measured since they are intimately related to the effective and intrinsic contact angles.

Conformational Transitions of Nucleic Acids under External Forces: Computer Simulations and a Stochastic Theory for their Kinetics

I will present molecular dynamics simulations of several examples of conformational transitions that nucleic acids and their complexes undergo upon the application of external forces and/or torques: (1) DNA supercoil relaxation by topoisomerases, (2) the condensation of DNA by dendrimers and, (3) RNA unfolding. Then I will showcase the use of the formalism of stochastic path integrals to deduce the kinetics of these transitions, from simulation trajectories or experimental single molecule recordings of the transition, under other conditions that those that are actually simulated or recorded.

Mechanical Force during Translocation by the Ribosome

Translocation of tRNA and mRNA by the ribosome during protein synthesis involves a number of precise and coordinated macromolecular rearrangements. Recently, high-resolution x-ray structures, cryo-EM reconstructions, and single-molecule fluorescence studies have yielded insight into the nature of these conformational states, and the kinetics of their inter-conversion. Yet, a detailed understanding of translocation is still missing mainly because its characterization requires the application of external force to inhibit or facilitate the step in which the ribosome converts chemical energy into mechanical work. Such measurements have so far remained elusive and, as a result, little is known about the mechanical properties of the ribosome, the maximum force it can exert during translocation, and its thermodynamic efficiency. Moreover, it is not known how the application of an external force affects the translocation rate, a response that is relevant to understanding the mechanism of translocation, co-translational protein folding, frameshifting, and other forms of translation regulation. Here, we address these questions using optical tweezers to follow translation by individual ribosomes along single mRNA molecules, against externally applied force. We find that the transition state during translocation is located close to the full extent of a one-codon step, ruling out models in which the mechanical step is composed of some combination of one- or two-nucleotide sub-steps. We show that the ribosome is able to generate a force barely sufficient to unwind the most stable structures typically found in mRNAs, making the translation rate highly sensitive to the presence and stability of these structures, and providing a mechanical basis for their regulatory role. Finally, our measurements indicate that the ribosome is able to convert the energy from the transpeptidation reaction into mechanical work with high efficiency. Our assay opens the way to characterizing the full mechano-chemical cycle of the ribosome.

Mechanical Regulation of Auxin-Mediated Growth

The phytohormone auxin is a primary regulator of growth and developmental pattern formation in plants. Auxin accumulates at specific sites (e.g., organ primordia) and induces localized growth within a tissue. Auxin also mediates developmental responses to intrinsic and external physical stimuli; however, exactly how mechanics influences auxin distribution is unknown. Here we show that mechanical strain can regulate auxin transport and accumulation in the tomato shoot apex, where new leaves emerge and rapidly grow. Modification of turgor pressure, application of external force, and artificial growth induction collectively show that the amount and intracellular localization of the auxin efflux carrier PIN1 are sensitive to mechanical alterations. In general, the more strained the tissue was, the more PIN1 was present per cell and the higher the proportion localized to the plasma membrane. Modulation of the membrane properties alone was sufficient to explain most of the mechanical effects. Our experiments support the hypothesis that the plasma membrane acts as a sensor of tissue mechanics that translates the cell wall strain into cellular responses, such as the intracellular localization of membrane-embedded proteins. One implication of this fundamental mechanism is the mechanical enhancement of auxin-mediated growth in young organ primordia. We propose that growth-induced mechanical strain upregulates PIN1 function and auxin accumulation, thereby promoting further growth, in a robust positive feedback loop.

Identification of Dominant Error Force Component in Hydraulic Pressure Reading for External Force Detection in Construction Manipulator

The purpose of this paper is to develop a fundamental external-force-detection framework for construction manipulators. Such an industrial application demands the practicality that satisfies detection requirements such as the accuracy and robustness while ensuring (i) a low cost, (ii) wide applicability, and (iii) a simple detection algorithm. For satisfying (i) and (ii), our framework first adopts a hydraulic sensor as a force sensor. However, hydraulic-pressure readings essentially include error force components. These components depend strongly on the joint kinetic state and differ in the identification difficulty owing to a nonlinear and uncertain hydromechanical system. For satisfying (ii) and (iii), our framework thus focuses on the dominant error-force components classified by the control input states, such as self-weight, cylinder driving, and oscillating forces, and identifies and removes them by using a theoreticalmodel, an experimental estimation, and a waveform analysis without complex modeling, respectively. Experiments were conducted using an instrumented hydraulic arm system. The results of a no-load task indicate that our framework greatly lowers the threshold to determine the on-off state of external force application, independent of the joint kinetic states. The results of an on-load task confirm that our framework robustly identifies the off states in which an external force is not applied to the hydraulic cylinder.

Membrane nanotubes induced by aqueous phase separation and stabilized by spontaneous curvature.

Tubular membrane structures are widespread in eukaryotic cells, but the mechanisms underlying their formation and stability are not well understood. Previous work has focused on tube extrusion from cells and model membranes under the application of external forces. Here, we present novel membrane/polymer systems, where stable tubes form in the absence of externally applied forces. Solutions of two water-soluble polymers, polyethylene glycol and dextran, were encapsulated in giant lipid vesicles, cell-size model systems. Hypertonic deflation induced phase separation of the enclosed solution. The excess membrane area created during the deflation process was stored in a large number of membrane nanotubes inside the vesicle. The tubes had a diameter below optical resolution and became visible only when fluorescently labeled. The tubes were rather stable: In the absence of external forces, they existed for several days. A theoretical analysis of the shapes of the deflated vesicles reveals that these shapes would be unstable if the membranes had no spontaneous curvature. Using the large separation of length scales between the tube diameter and the overall size of the vesicles, the spontaneous curvature can be calculated and is found to be about -1/(240 nm) for a certain range of polymer concentrations. The nanotubes could also be retracted back into the mother vesicle by increasing the membrane tension via micropipette aspiration of the vesicle. Membrane tubes, which can form and be retracted easily, should be relevant for lipid storage in cells.

Problems of studying an energetically active geologic medium

Deformations of the geologic medium are traditionally regarded as a result of the application of external forces. At the same time, such deformations can be realized at the expense of energy sources contained in the deformed bodies themselves. Since the idea of energetic inactivity of the medium dominates as an organizing center of scientific research in this field, it blocks the study of media in the state of energetic activity. The work discusses possible ways to overcome this conflict on the basis of specific examples.

Stem cell mechanobiology

Stem cells are undifferentiated cells that are capable of proliferation, self-maintenance and differentiation towards specific cell phenotypes. These processes are controlled by a variety of cues including physicochemical factors associated with the specific mechanical environment in which the cells reside. The control of stem cell biology through mechanical factors remains poorly understood and is the focus of the developing field of mechanobiology. This review provides an insight into the current knowledge of the role of mechanical forces in the induction of differentiation of stem cells. While the details associated with individual studies are complex and typically associated with the stem cell type studied and model system adopted, certain key themes emerge. First, the differentiation process affects the mechanical properties of the cells and of specific subcellular components. Secondly, that stem cells are able to detect and respond to alterations in the stiffness of their surrounding microenvironment via induction of lineage-specific differentiation. Finally, the application of external mechanical forces to stem cells, transduced through a variety of mechanisms, can initiate and drive differentiation processes. The coalescence of these three key concepts permit the introduction of a new theory for the maintenance of stem cells and alternatively their differentiation via the concept of a stem cell 'mechano-niche', defined as a specific combination of cell mechanical properties, extracellular matrix stiffness and external mechanical cues conducive to the maintenance of the stem cell population.

Description of consolidation forces on nanometric powders

The experiments and analyses performed included measurements of the physical properties of TiO2 powder such as the particle size, density, and consolidation. Experiments with nanometric TiO2powder of 204 nm average diameter show that, during consolidation, the adhesion of particles under normal stress is principally due to the van der Waals force for particle radii less than 300nm and the application of external force has no effect on the cohesion of the primary particles within this range; for particle radii around 300nm to 1.0µm the cohesion of the powder system is due to plastic deformation and the application of external force change the cohesion force to a plastic deformation between the agglomerates formed under these forces. This can be observed in the arrangement of the primary particles into dispersed agglomerates with sizes greater than the individual particles. The results obtained with the nanometric TiO2 powders show a more complex behavior than the micronic powders. This behavior is related to the structure of the nanometric particles in the packed bed; the evolution of this structure is made up of individualized and spherical agglomerate shapes. It has been experimentally observed that the powder structure is not perturbed by stresses of low intensities. A development of the different forces involved in interparticle contacts is outlined. The description of these forces involved in particle cohesion will help to understand the powder cohesion under consolidation.

Zyxin-mediated Actin Assembly Is Required for Efficient Wound Closure

Cytoskeletal regulation of cell adhesion is vital to the organization of multicellular structures. The focal adhesion protein zyxin emerged as a key regulator of actin assembly because zyxin recruits Enabled/vasodilator-stimulated phospho-proteins (Ena/VASP) to promote actin assembly. Zyxin also localizes to the sites of cell-cell adhesion and is thought to promote actin assembly with Ena/VASP. Using shRNA targeted to zyxin, we analyzed the roles of zyxin at adhesive contacts. In zyxin-deficient cells, the actin assembly at both focal adhesion and cell-cell adhesion was limited, but their migration rate was unchanged. Cell spreading on E-cadherin-coated surfaces and the formation of cell clusters were slower for zyxin-deficient cells than wild type cells. By ablating a single cell within a cell monolayer, we quantified the rate of wound closure driven by a contractile circumferential actin ring. Zyxin-deficient cells failed to recruit VASP to cell-cell junctions at the wound edge and had a slower wound closure rate than wild type cells. Our results suggest that, by recruiting VASP, zyxin regulates actin assembly at the sites of force-bearing cell-cell adhesion.

Blood flow restriction by low compressive force prevents disuse muscular weakness

Repetitive blood flow restriction prevents muscular atrophy and weakness induced by chronic unloading. However, it was unclear which external compressive force for blood flow restriction was optimal to prevent muscular dysfunction. The present study was intended to investigate the effects of repeated muscle blood flow restriction at low pressure on muscular weakness induced by immobilization without weight bearing. Using casts, the left ankles of 11 healthy males were immobilized for 2 weeks. Subjects were instructed to walk using crutches with no weight bearing during the period. Subjects were divided randomly into two groups: a restriction of blood flow (RBF) group (application of external compressive force of 50 mm Hg) and a control (CON) group (no intervention). We measured changes in the muscle strength of the knee extensor–flexor and ankle plantar flexor. The percent changes in knee extensor torque at 60°/s under eccentric contraction in the RBF group were significantly smaller than in the CON group (−12.5 ± 10.7% and −30.1 ± 10.9%, p < 0.05). The percent changes in knee flexor torque when performing an eccentric contraction at 60°/s, an isometric contraction, or a concentric contraction at both 60 and 300°/s in the RBF group were significantly smaller than those in the CON group ( p < 0.05). In conclusion, our results show that repetitive restriction of blood flow with 50 mm Hg cuff pressure to the lower extremity reduces muscular weakness induced by chronic unloading.