scholarly journals Digital virus manipulation chip with a large array of all-dielectric nanocavities

2021 ◽  
Author(s):  
Yuzhi Shi ◽  
Yongfeng Wu ◽  
Lip Ket Chin ◽  
Mu Ku Chen ◽  
Shubo Wang ◽  
...  
Keyword(s):  
Optical Tweezers ◽  
Antiviral Drug ◽  
Atomic Level ◽  
Aqueous Environment ◽  
Optical Forces ◽  
Cell Infection ◽  
Optical Cooling ◽  
Formidable Challenge ◽  
Wide Range ◽  
Virus Diagnostics

Abstract Spatial manipulation of a precise number of viruses for host cell infection is essential for the study of virus pathogenesis and evolution. Albeit optical tweezers have been advanced to the atomic level via optical cooling, it remains a formidable challenge to efficiently trap and move viruses in an aqueous environment, being restricted by insufficient strength of optical forces and a lack of precise spatial manipulation techniques. Here, we demonstrate giant optical forces produced by the enhancement of light in engineered arrays of nanocavities for trapping and digitally moving viruses down to 40 nm in size. By employing the virus hopping and flexibility of moving the laser position, we demonstrate a digital virus manipulation chip with a large trapping area, enabling single or massive virus transporting, positioning, and concentrating. Our work paves the way to efficient and precise manipulation of either single viruses or their massive ensembles, opening a wide range of novel opportunities for virus pathogenesis, virus diagnostics, vaccine, and antiviral drug development, being also important to tackle the current COVID-19 outbreaks.

scholarly journals Discovery of a Small Molecule Inhibitor of Human Adenovirus Capable of Preventing Escape from the Endosome

2021 ◽  
Vol 22 (4) ◽  
pp. 1617
Author(s):  
Jimin Xu ◽  
Judith Berastegui-Cabrera ◽  
Marta Carretero-Ledesma ◽  
Haiying Chen ◽  
Yu Xue ◽  
...  
Keyword(s):  
Potent Inhibitor ◽  
Antiviral Drug ◽  
Human Adenovirus ◽  
Yield Reduction ◽  
Respiratory Illnesses ◽  
Molecule Inhibitor ◽  
Wide Range ◽  
Ic50 Values ◽  
Life Threatening ◽  
Salicylamide Derivatives

Human adenoviruses (HAdVs) display a wide range of tissue tropism and can cause an array of symptoms from mild respiratory illnesses to disseminated and life-threatening infections in immunocompromised individuals. However, no antiviral drug has been approved specifically for the treatment of HAdV infections. Herein, we report our continued efforts to optimize salicylamide derivatives and discover compound 16 (JMX0493) as a potent inhibitor of HAdV infection. Compound 16 displays submicromolar IC50 values, a higher selectivity index (SI > 100) and 2.5-fold virus yield reduction compared to our hit compound niclosamide. Moreover, unlike niclosamide, our mechanistic studies suggest that the antiviral activity of compound 16 against HAdV is achieved through the inhibition of viral particle escape from the endosome, which bars subsequent uncoating and the presentation of lytic protein VI.

scholarly journals Stem–loop formation drives RNA folding in mechanical unzipping experiments

2022 ◽  
Vol 119 (3) ◽  
pp. e2025575119
Author(s):  
Paolo Rissone ◽  
Cristiano V. Bizarro ◽  
Felix Ritort
Keyword(s):  
Optical Tweezers ◽  
Rna Structure ◽  
Nearest Neighbor ◽  
Rna Folding ◽  
General Mechanism ◽  
Loop Formation ◽  
Stem Loop ◽  
Wide Range ◽  
Irreversible Effects ◽  
And Function

Accurate knowledge of RNA hybridization is essential for understanding RNA structure and function. Here we mechanically unzip and rezip a 2-kbp RNA hairpin and derive the 10 nearest-neighbor base pair (NNBP) RNA free energies in sodium and magnesium with 0.1 kcal/mol precision using optical tweezers. Notably, force–distance curves (FDCs) exhibit strong irreversible effects with hysteresis and several intermediates, precluding the extraction of the NNBP energies with currently available methods. The combination of a suitable RNA synthesis with a tailored pulling protocol allowed us to obtain the fully reversible FDCs necessary to derive the NNBP energies. We demonstrate the equivalence of sodium and magnesium free-energy salt corrections at the level of individual NNBP. To characterize the irreversibility of the unzipping–rezipping process, we introduce a barrier energy landscape of the stem–loop structures forming along the complementary strands, which compete against the formation of the native hairpin. This landscape correlates with the hysteresis observed along the FDCs. RNA sequence analysis shows that base stacking and base pairing stabilize the stem–loops that kinetically trap the long-lived intermediates observed in the FDC. Stem–loops formation appears as a general mechanism to explain a wide range of behaviors observed in RNA folding.

scholarly journals Micromanipulation of mitotic chromosomes in PTK2 cells using laser-induced optical forces (“optical tweezers”)

1991 ◽  
Vol 197 (1) ◽  
pp. 21-35 ◽  
Author(s):  
Hong Liang ◽  
William H. Wright ◽  
Wei He ◽  
Michael W. Berns
Keyword(s):  
Optical Tweezers ◽  
Optical Forces ◽  
Mitotic Chromosomes

scholarly journals Construction of 3D Cellular Composites with Stem Cells Derived from Adipose Tissue and Endothelial Cells by Use of Optical Tweezers in a Natural Polymer Solution

Materials ◽  
2019 ◽  
Vol 12 (11) ◽  
pp. 1759 ◽  
Author(s):  
Takehiro Yamazaki ◽  
Toshifumi Kishimoto ◽  
Paweł Leszczyński ◽  
Koichiro Sadakane ◽  
Takahiro Kenmotsu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Adipose Tissue ◽  
Optical Tweezers ◽  
Single Cells ◽  
Three Dimensional ◽  
Cell Types ◽  
Cellular Interactions ◽  
Research Fields ◽  
Wide Range

To better understand the regulation and function of cellular interactions, three-dimensional (3D) assemblies of single cells and subsequent functional analysis are gaining popularity in many research fields. While we have developed strategies to build stable cellular structures using optical tweezers in a minimally invasive state, methods for manipulating a wide range of cell types have yet to be established. To mimic organ-like structures, the construction of 3D cellular assemblies with variety of cell types is essential. Our recent studies have shown that the presence of nonspecific soluble polymers in aqueous solution is the key to creating stable 3D cellular assemblies efficiently. The present study further expands on the construction of 3D single cell assemblies using two different cell types. We have successfully generated 3D cellular assemblies, using GFP-labeled adipose tissue-derived stem cells and endothelial cells by using optical tweezers. Our findings will support the development of future applications to further characterize cellular interactions in tissue regeneration.

scholarly journals Feedback traps for virtual potentials

2017 ◽  
Vol 375 (2088) ◽  
pp. 20160217 ◽  
Author(s):  
Momčilo Gavrilov ◽  
John Bechhoefer
Keyword(s):  
Optical Tweezers ◽  
Single Molecule ◽  
Feedback Loop ◽  
Target Object ◽  
Optical Forces ◽  
First Law Of Thermodynamics ◽  
Average Work ◽  
Arbitrary Potential ◽  
Information Erasure ◽  
Long Protocol

Feedback traps are tools for trapping and manipulating single charged objects, such as molecules in solution. An alternative to optical tweezers and other single-molecule techniques, they use feedback to counteract the Brownian motion of a molecule of interest. The trap first acquires information about a molecule's position and then applies an electric feedback force to move the molecule. Since electric forces are stronger than optical forces at small scales, feedback traps are the best way to trap single molecules without ‘touching’ them (e.g. by putting them in a small box or attaching them to a tether). Feedback traps can do more than trap molecules: they can also subject a target object to forces that are calculated to be the gradient of a desired potential functionU(x). If the feedback loop is fast enough, it creates avirtual potentialwhose dynamics will be very close to those of a particle in an actual potentialU(x). But because the dynamics are entirely a result of the feedback loop—absent the feedback, there is only an object diffusing in a fluid—we are free to specify and then manipulate in time an arbitrary potentialU(x,t). Here, we review recent applications of feedback traps to studies on the fundamental connections between information and thermodynamics, a topic where feedback plays an even more fundamental role. We discuss how recursive maximum-likelihood techniques allow continuous calibration, to compensate for drifts in experiments that last for days. We consider ways to estimate work and heat, using them to measure fluctuating energies to a precision of ±0.03kTover these long experiments. Finally, we compare work and heat measurements of the costs of information erasure, theLandauer limitofkTln 2 per bit of information erased. We argue that, when you want to know the average heat transferred to a bath in a long protocol, you should measure instead the average work and then infer the heat using the first law of thermodynamics.This article is part of the themed issue ‘Horizons of cybernetical physics’.

Computational Coevolution of Antiviral Drug Resistance

1998 ◽  
Vol 4 (1) ◽  
pp. 41-59 ◽  
Author(s):  
Christopher D. Rosin ◽  
Richard K. Belew ◽  
Garrett M. Morris ◽  
Arthur J. Olson ◽  
David S. Goodsell
Keyword(s):  
Drug Resistance ◽  
Broad Class ◽  
Antiviral Drug ◽  
Resistant Mutant ◽  
Approximate Model ◽  
Cross Resistance ◽  
Resistance Mutations ◽  
Wide Range ◽  
Antiviral Drug Resistance ◽  
Mutant Forms

An understanding of antiviral drug resistance is important in the design of effective drugs. Comprehensive features of the interaction between drug designs and resistance mutations are difficult to study experimentally because of the very large numbers of drugs and mutants involved. We describe a computational framework for studying antiviral drug resistance. Data on HIV-1 protease are used to derive an approximate model that predicts interaction of a wide range of mutant forms of the protease with a broad class of protease inhibitors. An algorithm based on competitive coevolution is used to find highly resistant mutant forms of the protease, and effective inhibitors against such mutants, in the context of the model. We use this method to characterize general features of inhibitors that are effective in overcoming resistance, and to study related issues of selection pathways, cross-resistance, and combination therapies.

Atomic level simulations of the interaction of asphaltene with quartz surfaces: role of chemical modifications and aqueous environment

2016 ◽  
Vol 50 (1) ◽  
Author(s):  
Naresh K. Jena ◽  
Åsa Laurell Lyne ◽  
N. Arul Murugan ◽  
Hans Ågren ◽  
Björn Birgisson
Keyword(s):  
Atomic Level ◽  
Aqueous Environment ◽  
Chemical Modifications

Microfluidics Supporting an Optical Instrument for Multimodal Single Cell Biomechanics

2007 ◽  
Author(s):  
Nathalie Ne`ve ◽  
James K. Lingwood ◽  
Shelley R. Winn ◽  
Derek C. Tretheway ◽  
Sean S. Kohles
Keyword(s):  
Particle Image Velocimetry ◽  
Hydrostatic Pressure ◽  
Single Cell ◽  
Optical Tweezers ◽  
Particle Image ◽  
Single Cells ◽  
Optical Instrument ◽  
Image Velocimetry ◽  
Wide Range ◽  
Induced Stresses

Interfacing a novel micron-resolution particle image velocimetry and dual optical tweezers system (μPIVOT) with microfluidics facilitates the exposure of an individual biologic cell to a wide range of static and dynamic mechanical stress conditions. Single cells can be manipulated in a sequence of mechanical stresses (hydrostatic pressure variations, tension or compression, as well as shear and extensional fluid induced stresses) while measuring cellular deformation. The unique multimodal load states enable a new realm of single cell biomechanical studies.

Optical forces on arbitrary shaped particles in optical tweezers

2010 ◽  
Vol 108 (7) ◽  
pp. 073110 ◽  
Author(s):  
Lin Ling ◽  
Fei Zhou ◽  
Lu Huang ◽  
Zhi-Yuan Li
Keyword(s):  
Optical Tweezers ◽  
Optical Forces
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