Surfactants modify the torsion properties of proteins: a single molecule study

Gutiérrez-Mejía, Fabiola A.; IJzendoorn, L.J. van; Prins, Mwj Menno

doi:10.1016/j.nbt.2015.02.005

Cited by 7 publications

(6 citation statements)

References 40 publications

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“…Several blocking agents can be employed to avoid or greatly decrease nonspecific adsorption on the sensor surface. Previous studies have demonstrated that coating of the sensor surface with PLL- g -PEG and the presence of surfactant agent Tween 20 in the detection buffer, minimizes the background signal produced by undiluted urine. − Based on this, we have studied the effect of different concentrations of blocking agents in order to reduce nonspecific adsorption when flowing urine from a healthy patient over the sensors were we have previously immobilized the anti-LAM antibody: (i) 10 mg/mL BSA, (ii) 0.5 mg/mL PLL- g -PEG, and (iii) 0.75 mg/mL PLL- g -PEG and 10 mg/mL BSA. First, an undiluted urine sample from a healthy donor was injected on the surface blocked with 10 mg/mL BSA and resulted in a background signal of 1.27 nm.…”

Section: Resultsmentioning

confidence: 99%

Label-Free and Real-Time Detection of Tuberculosis in Human Urine Samples Using a Nanophotonic Point-of-Care Platform

et al. 2018

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Tuberculosis (TB) is the leading global cause of death from a single infectious agent. Registered incidence rates are low, especially in low-resource countries with weak health systems, due to the disadvantages of current diagnostic techniques. A major effort is directed to develop a point-of-care (POC) platform to reduce TB deaths with a prompt and reliable low-cost technique. In the frame of the European POCKET Project, a novel POC platform for the direct and non-invasive detection of TB in human urine was developed. The photonic sensor is integrated in a disposable cartridge and is based on a highly sensitive Mach-Zehnder Interferometer (MZI) transducer combined with an on-chip spectral filter. The required elements for the read-out are integrated in an instrument prototype, which allows real-time monitoring and data processing. In this work, the novel POC platform has been employed for the direct detection of lipoarabinomannan (LAM), a lipopolysaccharide found in the mycobacterium cell wall. After the optimization of several parameters, a limit of detection of 475 pg/mL (27.14 pM) was achieved using a direct immunoassay in undiluted human urine in less than 15 minutes. A final validation of the technique was performed using twenty clinical samples from TB patients and healthy donors, allowing the detection of TB in people regardless of HIV coinfection. The results show excellent correlation to those obtained with standard techniques. These promising results demonstrate the high sensitivity, specificity and applicability of our novel POC platform, which could be used during routine checkups in developing countries.

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Section: Resultsmentioning

confidence: 99%

Label-Free and Real-Time Detection of Tuberculosis in Human Urine Samples Using a Nanophotonic Point-of-Care Platform

et al. 2018

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“…131,132 The system was used to study the torsional properties of proteins as a function of the angle of rotation 70 and as a function of the concentration of surfactants. 77 Fluorescent nanoparticles were attached to the MP for angular tracking, see Fig. 8.…”

Section: Biophysical Characterizationmentioning

confidence: 99%

Rotating magnetic particles for lab-on-chip applications – a comprehensive review

2019

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“…We note that in reality the solvent properties (e.g., surfactants) affect the torsional properties of proteins. As Gutiérrez-Mejía et al [6] show, the presence of surfactants does not significantly affect the proteins' structure, it may however induce a local denaturation near a binding site. Since our domain of interest is not near a binding site, we assume that it is not significantly affected by the presence (or absence) of a surfactant.…”

Section: Atomistic Simulation Using Molecular Dynamics (Md)mentioning

confidence: 99%

“…Not only can these particles serve as labels for the analytes, but upon actuation with magnetic fields they can be actively manipulated and be used to, e.g., mix fluids within the sensor. In addition, the magnetic particles may act as magnetic tweezers in order to exert forces on the molecules [4][5][6]. This experimental method is used to study the structural properties and unfold-ing of molecules such as proteins, DNA and RNA [7][8][9][10][11], and may be employed side-by-side with atomic force microscopy (AFM) [12][13][14][15][16] and optical tweezers [17][18][19][20][21][22] experiments to assess the mechanical properties of molecules.…”

Section: Introductionmentioning

confidence: 99%

Combined Force-Torque Spectroscopy of Proteins by Means of Multiscale Molecular Simulation

Heijden

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Harlen

et al. 2020

Biophysical Journal

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Assessing the structural properties of large proteins is important to gain an understanding of their function in, e.g., biological systems or biomedical applications. We propose a method to examine the mechanical properties of proteins subject to applied forces by means of multiscale simulation. Both stretching and torsional forces are considered, and these may be applied independently of each other. As a proof of principle, we apply torsional forces to a coarse-grained continuum model of the antibody protein immunoglobulin G (IgG) using Fluctuating Finite Element Analysis and use it to identify the area of strongest deformation. This region is essential to the torsional properties of the molecule as a whole, as it represents the softest, most deformable domain. Zooming in, this part of the molecule is subjected to torques and stretching forces using molecular dynamics simulations on an atomistically resolved level, in order to investigate its torsional properties. We calculate the torsional resistance as a function of the rotation of the domain, while subjecting it to various stretching forces. From this, we assess how the measured twist-torque profiles develop with increasing stretching force, and show that they exhibit torsion stiffening, in qualitative agreement with experimental findings. We argue that combining the twist-torque profiles for various stretching forces effectively results in a combined force-torque spectroscopy analysis, which may serve as a mechanical signature for a biological macromolecule.SIGNIFICANCE In this work, we propose a multiscale numerical approach to assess the mechanical properties of macromolecules such as proteins. We perform a combined force-torque spectroscopy analysis on the mechanically most relevant domain to compute the response signature of the spatial structure of the macromolecule. This information may lead to a better understanding of molecular structure and function in biological context and may be used towards diagnostic and sensing applications in the biomedical field.

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Surfactants modify the torsion properties of proteins: a single molecule study

Cited by 7 publications

References 40 publications

Label-Free and Real-Time Detection of Tuberculosis in Human Urine Samples Using a Nanophotonic Point-of-Care Platform

Label-Free and Real-Time Detection of Tuberculosis in Human Urine Samples Using a Nanophotonic Point-of-Care Platform

Rotating magnetic particles for lab-on-chip applications – a comprehensive review

Combined Force-Torque Spectroscopy of Proteins by Means of Multiscale Molecular Simulation

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