scholarly journals Quantification of fast molecular adhesion by fluorescence footprinting

2021 ◽  
Vol 7 (34) ◽  
pp. eabe6984
Author(s):  
Adam B. Yasunaga ◽  
Isaac T. S. Li
Keyword(s):  
Shear Stress ◽  
Dynamic Range ◽  
Force Distribution ◽  
Receptor Ligand ◽  
Ligand Dissociation ◽  
Molecular Adhesion ◽  
Molecular Force ◽  
Nonequilibrium Conditions ◽  
Adhesion Complex

Rolling adhesion is a unique process in which the adhesion events are short-lived and operate under highly nonequilibrium conditions. These characteristics pose a challenge in molecular force quantification, where in situ measurement of these forces cannot be achieved with molecular force sensors that probe near equilibrium. Here, we demonstrated a quantitative adhesion footprint assay combining DNA-based nonequilibrium force probes and modeling to measure the molecular force involved in fast rolling adhesion. We were able to directly profile the ensemble molecular force distribution in our system during rolling adhesion with a dynamic range between 0 and 18 pN. Our results showed that the shear stress driving bead rolling motility directly controls the molecular tension on the probe-conjugated adhesion complex. Furthermore, the shear stress can steer the dissociation bias of components within the molecular force probe complex, favoring either DNA probe dissociation or receptor-ligand dissociation.

scholarly journals Quantification of fast molecular adhesion by fluorescence footprinting

2021 ◽  
Author(s):  
Adam B. Yasunaga ◽  
Isaac T.S. Li
Keyword(s):  
Shear Stress ◽  
Dynamic Range ◽  
Force Distribution ◽  
Equilibrium Conditions ◽  
Ligand Dissociation ◽  
Molecular Adhesion ◽  
Molecular Force ◽  
Adhesion Complex ◽  
Non Equilibrium

AbstractRolling adhesion is a unique process in which the adhesion events are short-lived and operate under highly non-equilibrium conditions. These characteristics pose a challenge in molecular force quantification, where in situ measurement of such forces cannot be achieved with most molecular force sensors that probe near equilibrium. In this report, we demonstrated a quantitative adhesion footprint assay combining DNA-based non-equilibrium force probes and modelling to measure the molecular force involved in fast rolling adhesion. We were able to directly profile the ensemble molecular force distribution during rolling adhesion with a dynamic range between 0 – 18 pN. Our results showed that the shear stress driving bead rolling motility directly controls the molecular tension on the probe-conjugated adhesion complex. Furthermore, the shear stress can steer the dissociation bias of components within the molecular force probe complex, favouring either DNA probe dissociation or receptor-ligand dissociation.

scholarly journals Quantifying Molecular Forces with Serially Connected Force Sensors

2018 ◽  
Author(s):  
Y. Murad ◽  
I. T.S. Li
Keyword(s):  
Cell Adhesion ◽  
Dynamic Range ◽  
Computational Study ◽  
Experimental Studies ◽  
High Signal ◽  
Force Sensors ◽  
Adhesion Forces ◽  
Receptor Ligand ◽  
Sequence Composition ◽  
Molecular Force

AbstractTo understand the mechanical forces involved in cell adhesion, molecular force sensors have been developed to study tension through adhesion proteins. Recently, a class of molecular force sensors called tension gauge tether (TGT) have been developed that rely on irreversible force-dependent dissociation of DNA duplex to study cell adhesion forces. While the TGT offer high signal-to-noise ratio and is ideal for studying fast / single molecular adhesion processes, quantitative interpretation of experimental results has been challenging. Here we used computational approach to investigate how TGT fluorescence readout can be quantitatively interpreted. In particular we studied force sensors made of a single TGT, multiplexed single TGTs, and two TGTs connected in series. Our results showed that fluorescence readout using a single TGT can result from drastically different combinations of force history and adhesion event density that span orders of magnitude. In addition, the apparent behaviour of the TGT is influenced by the tethered receptor-ligand, making it necessary to calibrate the TGT with every new receptor-ligand. To solve this problem, we proposed a system of two serially connected TGTs. Our result shows that not only is the ratiometric readout of serial TGT independent of the choice of receptor-ligand, it is able to reconstruct force history with sub-pN force resolution. This is also not possible by simply multiplexing different types of TGTs together. Lastly, we systematically investigated how sequence composition of the two serially connected TGTs can be tuned to achieve different dynamic range. This computational study demonstrated how serially connected irreversible molecular dissociation processes can accurately quantify molecular force, and laid the foundation for subsequent experimental studies.

A NEW ORGANIC/INORGANIC HYBRID WITH HIGH ELECTRORHEOLOGICAL ACTIVITY

2002 ◽  
Vol 16 (17n18) ◽  
pp. 2454-2460 ◽  
Author(s):  
X. P. ZHAO ◽  
X. DUAN
Keyword(s):  
Activation Energy ◽  
Shear Stress ◽  
Necessary Conditions ◽  
Sol Gel ◽  
Root Temperature ◽  
Sedimentation Stability ◽  
Inorganic Hybrid ◽  
Active Particles ◽  
Static Shear

In-situ sol-gel method to prepare colloidal hybrids of surfactant modified polysucchride and titanium oxide has been presented, and experiments indicated these highly ER active particles exhibited a remarkable ER effect. The static shear stress can be up to 37 k Pa (shear rate 5 S -1) under DC field of 4 kV/mm at root temperature, well above that of simple blends of starch and TiO 2. In the meanwhile, temperature dependence and sedimentation stability were also greatly improved. Based on recent experimental facts, we find that dielectric properties and surface (interface) activity are two necessary conditions fulfilling the requirement of high ER activity. Adequate grinding of particles with oil can effectively enhance the shear stress, which may be owed to the decline of the activation energy needed for restructuring. It has provided us a new horizon for preparation of excellent ER materials and further studies should be continued to make.

scholarly journals Robust Calorimetric Micro-Sensor for Aerodynamic Applications

Proceedings ◽  
2018 ◽  
Vol 2 (13) ◽  
pp. 794
Author(s):  
Cécile Ghouila-Houri ◽  
Célestin Ott ◽  
Romain Viard ◽  
Quentin Gallas ◽  
Eric Garnier ◽  
...  
Keyword(s):  
Shear Stress ◽  
Flow Control ◽  
Flow Separation ◽  
Active Flow Control ◽  
Small Length ◽  
High Frequencies ◽  
Small Length Scale ◽  
Micro Sensor ◽  
Active Flow

This paper reports a calorimetric micro-sensor designed for aerodynamic applications. Measuring both the amplitude and the sign of the wall shear stress at small length-scale and high frequencies, the micro-sensor is particularly suited for flow separation detection and flow control. The micro-sensor was calibrated in static and dynamic in a turbulent boundary layer wind tunnel. Several micro-sensors were embedded in various configurations for measuring the shear stress and detecting flow separation. Specially, one was embedded inside an actuator slot for in situ measurements and twelve, associated with miniaturized electronics, were implemented on a flap model for active flow control experiments.

A critical look at the Wallace-Bott hypothesis in fault-slip analysis

2013 ◽  
Vol 184 (4-5) ◽  
pp. 299-306 ◽  
Author(s):  
Richard J. Lisle
Keyword(s):  
Shear Stress ◽  
Maximum Shear Stress ◽  
Fault Slip ◽  
Shear Stresses ◽  
Homogeneous State ◽  
Slip Direction ◽  
Fault Surface ◽  
State Of Stress ◽  
Simultaneous Movement

AbstractThe assumption is widely made that slip on faults occurs in the direction of maximum resolved shear stress, an assumption known as the Wallace-Bott hypothesis. This assumption is used to theoretically predict slip directions from known in situ stresses, and also as the basis of palaeostress inversion from fault-slip data. This paper examines different situations in relation to the appropriateness of this assumption. Firstly, it is shown that the magnitude of the shear stress resolved within a plane is a function with a poorly defined maximum direction, so that shear stress values greater than 90% of the maximum occur within a wide angular range (± 26°) degrees. The situation of simultaneous movement on pairs of faults requires slip on each fault to be parallel to their mutual line of intersection. However, the resolved shear stresses arising from a homogeneous state of stress do not accord with such a slip arrangement except in the case of pairs of perpendicular faults. Where fault surfaces are non-planar, the directions of resolved shear stress in general give, according to the Wallace-Bott hypothesis, a set of slip directions of rigid fault blocks, which is generally kinematically incompatible. Finally, a simple model of a corrugated fault suggests that any anisotropy of the shear strength of the fault such as that arising from fault surface topography, can lead to a significant angular difference between the directions of maximum shear stress and the slip direction.These findings have relevance to the design of procedures used to estimate palaeostresses and the amount of data required for this type of analysis.

scholarly journals Prediction of Boundary Shear Stress Distribution in Converging Compound Channel Using Gene Expression Programming

2022 ◽  
Author(s):  
Bandita Naik ◽  
Vijay Kaushik ◽  
Munendra Kumar
Keyword(s):  
Shear Stress ◽  
Stress Distribution ◽  
Shear Force ◽  
Gene Expression Programming ◽  
Main Channel ◽  
Shear Stress Distribution ◽  
Force Distribution ◽  
Compound Channel ◽  
Boundary Shear ◽  
Boundary Shear Stress

Abstract The computation of the boundary shear stress distribution in an open channel flow is required for a variety of applications, including the flow resistance relationship and the construction of stable channels. The river breaches the main channel and spills across the floodplain during overbank flow conditions on both sides. Due to the momentum shift between the primary channel and adjacent floodplains, the flow structure in such compound channels becomes complicated. This has a profound impact on the shear stress distribution in the floodplain and main channel subsections. In addition, agriculture and development activities have occurred in floodplain parts of a river system. As a consequence, the geometry of the floodplain changes over the length of the flow, resulting in a converging compound channel. Traditional formulas, which rely heavily on empirical approaches, are ineffective in predicting shear force distribution with high precision. As a result, innovative and precise approaches are still in great demand. The boundary shear force carried by floodplains is estimated by gene expression programming (GEP) in this paper. In terms of non-dimensional geometric and flow variables, a novel equation is constructed to forecast boundary shear force distribution. The proposed GEP-based method is found to be best when compared to conventional methods. The findings indicate that the predicted percentage shear force carried by floodplains determined using GEP is in good agreement with the experimental data compared to the conventional formulas (R2 = 0.96 and RMSE = 3.395 for the training data and R2 = 0.95 and RMSE = 4.022 for the testing data).

scholarly journals Novel Electrochemiluminescent Assays for Drug Discovery

2000 ◽  
Vol 5 (1) ◽  
pp. 45-48 ◽  
Author(s):  
Maura C. Kibbey ◽  
David MacAllan ◽  
James W. Karaszkiewicz
Keyword(s):  
Drug Discovery ◽  
High Precision ◽  
High Throughput ◽  
High Performance ◽  
Dynamic Range ◽  
Wide Dynamic Range ◽  
Receptor Ligand ◽  
Enzymatic Assays ◽  
Detection Systems ◽  
Protein Assays

IGEN's ORIGEN® technology, which is based on electrochemiluminescence, has been adopted by a number of research and bioanalytical laboratories who have recognized its exquisite sensitivity, high precision, wide dynamic range, and flexibility in formatting a wide variety of applications. IGEN's M-SERIES™ marks the introduction of the second generation of detection systems employing the ORIGEN technology specifically repackaged to address the needs of the high throughput laboratories involved in drug discovery. Assays are formatted without wash steps. Users realize the high performance of a heterogeneous technology with the convenience of a homogeneous format. The M-SERIES platform can address enzymatic assays (kinases, proteases, helicases, etc.), receptor-ligand or protein-protein assays, immunoassays, quantitation of nucleic acids, as well as other applications. Recent assay formats will be explored in detail.

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