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What can you do with Optical Tweezers in Life Sciences?

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Motivation

Optical Tweezers is a very useful tool in life sciences that uses laser beams to grab and move tiny particles like beads, cells, organelles, DNA, and proteins. It helps scientific researchers to study how these particles behave and interact, allowing them to explore things at a much smaller level than before. Even though Optical Tweezers has many important uses in biology and medicine, not many people know about it or understand what it can do in life sciences.

This post is designed for readers who are either unfamiliar or somewhat familiar with the topic of Optical Tweezers, providing a catalog of Optical Tweezers applications in life sciences. Every section contains several applications drawn from selected peer-reviewed publications.

This post aims to expand reader’s general knowledge about Optical Tweezers applications in life science. For individuals who are very familiar with the field or experts, we recommend exploring more specialized sources for advanced insights and technical details.

After reading all the applications, we recommend readers to read this link to discover the innovative MMI solution for Optical Tweezers system.

Applications with Optical Tweezers

 

Catalog of Applications

Cell-based studies: Cell interactions

Studying cell interactions is crucial for combating diseases because it helps us understand how cells communicate, cooperate, or conflict within the body. Many diseases, such as cancer, infections, and autoimmune disorders, result from disruptions in normal cell interactions. By examining how cells interact with each other and their environment, researchers can identify the underlying mechanisms that cause disease, develop targeted treatments, and improve drug delivery.

Here are several Optical Tweezers applications in studying cell interactions:

  1. Immune Cell-Pathogen Interactions Study: Svoboda, K., Block, S. M. (1994). Biological applications of optical forces. Annual Review of Biophysics and Biomolecular Structure, 23, 247-285. https://doi.org/10.1146/annurev.bb.23.060194.001335

Focus: Examines Optical Tweezers for manipulating immune cells to study interactions with pathogens.

  1. Red Blood Cell Aggregation Study: Dao, M., Lim, C. T., & Suresh, S. (2003). Mechanics of the human red blood cell deformed by Optical Tweezers. Journal of the Mechanics and Physics of Solids, 51(11-12), 2259-2280. https://doi.org/10.1016/j.jmps.2003.09.019

Focus: Investigates red blood cell mechanical properties using Optical Tweezers to understand cell aggregation.

  1. T-Cell and Antigen-Presenting Cell Interaction Study: Wei, X et al (1999). Mapping the sensitivity of T cells with an optical trap: Polarity and minimal number of receptors for Ca2+ signaling. PNAS, 96(15), 8471–8476. 1073/pnas.96.15.8471

Focus: Describes the use of Optical Tweezers in studying T-cell interactions with antigen-presenting cells.

  1. Bacterial Adhesion to Host Cells Study: Ashkin, A., Dziedzic, J. M., & Yamane, T. (1987). Optical trapping and manipulation of single cells using infrared laser beams. Nature, 330(6150), 769-771. 1038/330769a0

Focus: Optical Tweezers are used to study how bacteria adhere to host cells.

  1. Cell-Cell Adhesion in Cancer Metastasis Study: Xu, J., Tseng, Y., & Wirtz, D. (2000). Strain hardening of actin filament networks: Regulation by the dynamic cross-linking protein α-actinin. Journal of Biological Chemistry, 275(46), 35886-35892. 1074/jbc.M002377200

Focus: Examines cell adhesion and mechanics in cancer metastasis using Optical Tweezers.

  1. Phagocytic Cells – Microbe Interaction Study: Tam et al. (2010). Control and Manipulation of Pathogens with an Optical Trap for Live Cell Imaging of Intercellular Interactions. PLoS ONE 5(12): e15215. https://doi.org/10.1371/journal.pone.0015215

Focus: Describes the use of Optical Tweezers and live cell imaging to study the dynamic interactions between cells of the immune system

  1. Fibroblast – Fibronectin Coated Bead Interaction Study: Choquet et al (1997). Extracellular Matrix Rigidity Causes Strengthening of Integrin–Cytoskeleton Linkages. Cell. Vol 88, Issue 1, P39-48. https://doi.org/10.1016/S0092-8674(00)81856-5

Focus: Uses Optical Tweezers to investigate whether cells respond to the rigidity of the anchoring matrix.

  1. Sperm – Egg Interaction Study: Clement-Sengewald et al (1996). Fertilization of Bovine Oocytes Induced Solely with Combined Laser Microbeam and Optical Tweezers. Journal of Assisted Reproduction and Genetics, Vol. 13, No. 3, 259-265. https://doi.org/10.1007/BF02065947

Focus: Uses combined Optical Tweezers and UV-laser microbeam to perform “non-contact” microinsemination procedures.

  1. Human Natural Killer Cells (NK) – Human Erytholeukemia (K562) Interaction Study: Seeger et al (1991). Application of laser Optical Tweezers in immunology and molecular genetics. Cytometry, 12(6):497-504. 1002/cyto.990120606

Focus: Uses Optical Tweezers to establish contact between killer cells and their target cells.

  1. Cilia – Fluid Flow Interaction (Cell – Environment Interaction) Study: Katoh et al (2023). Immotile cilia mechanically sense the direction of fluid flow for left-right determination. Science, Vol. 379, Issue 6627 page 66-71. DOI: 10.1126/science.abq8148

Focus: Uses Optical Tweezers to observe if immotile cilia sense the mechanical force generated by the flow and suggest a biophysical mechanism by which the direction of the flow is sensed.

 

Cell-based studies: Intracellular manipulations

The ability to manipulate cell organelles is crucial to understand disease mechanism. Diseases like neurogenerative disorders and cancers are linked to organelle dysfunction. Researchers can use Optical Tweezers to model dysfunctions by altering organelle position, providing insights into how diseases develop at the cellular level.

Here are several Optical Tweezers applications in manipulating intracellular components and organelles:

  1. Plant Organelles Manipulation Study: Hawes et al (2010). Optical Tweezers for the micromanipulation of plant cytoplasm and organelles. Curr Opin Plant Biol. 13(6):731-5. 10.1016/j.pbi.2010.10.004

It focuses on how to trap and manipulate organelles within the cytoplasm and remodel the architecture of the cytoplasm and membrane systems.

  1. Golgi Bodies Manipulation in Plant Cells Study: Sparkes et al (2009). Grab a Golgi: laser trapping of Golgi bodies reveals in vivo interactions with the endoplasmic reticulum. Traffic. 10(5):567-71. 10.1111/j.1600-0854.2009.00891.x

Investigates how the displacement of individual Golgi bodies is associated with the endoplasmic reticulum.

  1. Chloroplast Manipulation in Plant Cells Study: Bayoudh et al (2001). Micromanipulation of chloroplasts using Optical Tweezers. J Microsc. 203(Pt 2):214-22. 10.1046/j.1365-2818.2001.00843.x

It uses Optical Tweezers to probe chloroplast arrangement, shape and consistency in cells of living leaf tissue and in suspension

  1. Amyloplast Manipulation in Plant Cells Study: Abe et al (2020). Micromanipulation of amyloplasts with Optical Tweezers in Arabidopsis stems. Plant Biotechnol (Tokyo). 37(4): 405-415. 10.5511/plantbiotechnology.20.1201a

It uses Optical Tweezers to study the controlled movement of amyloplast influencing the gravity-sensing mechanism in plants.

  1. Peroxisome Manipulation in Plant Cells Study: Gao et al (2016). In Vivo Quantification of Peroxisome Tethering to Chloroplasts in Tobacco Epidermal Cells Using Optical Tweezers. Plant Physiology. Vol. 170, Issue 1, Pages 263-272. https://doi.org/10.1104/pp.15.01529

It uses Optical Tweezers to trap peroxisomes and approximate the forces involved in the chloroplast association.

  1. Neuronal Mitochondria Manipulation Study: Gong et al (2023). Optical manipulation of neuronal mitochondria using

scanning Optical tweezers. Journal of Innovative Optical Health Science, 98(2). https://dx.doi.org/10.1142/S1793545823410018

It focuses on how Optical Tweezers is used to artificially control the transport of neuronal mitochondria.

  1. Transfer Mitochondria from Fetal to Adult Mesenchymal Stem Cells Study: Shakoor et al (2021). Automated Optical Tweezers Manipulation to Transfer Mitochondria from Fetal to Adult MSCs to Improve Antiaging Gene Expressions. Small.

It uses automated Optical Tweezers-based system to transfer healthy mitochondria from Fetal to Adult to reverse the aging-related phenotype.

  1. Controlling Nuclei Positioning Study: Du et al (1991). Laser tweezer manipulation of micronuclei in Paramecium. OSA Annual Meeting 1991. https://doi.org/10.1364/OAM.1991.WG5

It uses Optical Tweezers to control the position of the nuclei in the context of observing its influence on the growth and reproduction of Paramecia.

  1. Chromosomes and Mitotic Spindle Manipulation Study: Berns et al (2006). Chapter 36 – Micromanipulation of Chromosomes and the Mitotic Spindle Using Laser Microsurgery (Laser Scissors) and Laser-Induced Optical Forces (Laser Tweezers). Cell Biology (3rd Ed.) A Laboratory Handbook. Vol.3, pages 351-363. https://doi.org/10.1016/B978-012164730-8/50164-7

It uses combined methods such as Optical Tweezers, pulsed lasers, and fluorescent labeled proteins to selectively manipulate individual chromosomes to perform genetic studies.

  1. Manipulation of Filamentous Fungi Organelles Study: Wright et al (2007). Optical tweezer micromanipulation of filamentous fungi. Fungal Genetics and Biology. 44, pages 1-13. https://doi.org/10.1016/j.fgb.2006.07.002

It uses Optical Tweezers to trap whole fungal N. crassa cells, organelles within cells, and beads.

 

in vivo Micromanipulations

Using Optical Tweezers in vivo offers a non-invasive, precise, and highly controlled way to study complex biological systems. It opens new possibilities for investigating the physical forces and interactions driving essential life processes, all while maintaining the integrity of the living organism.

Here are several Optical Tweezers applications in in vivo  micromanipulations:

  1. Cell Manipulation Inside Living Zebrafish Study: Johansen et al. (2016). Optical micromanipulation of nanoparticles and cells inside living zebrafish. comm. 7:10974. DOI: 10.1038/ncomms10974

It shows that different cells, injected nanoparticles, and bacteria can be trapped inside living zebrafish.

  1. Manipulating Injected Fluorescent Beads Inside Living Zebrafish Embryos Study: Hoerner et al. (2017). Holographic Optical Tweezers-based in vivo manipulations in zebrafish embryos. Journal of Biophotonics. https://doi.org/10.1002/jbio.201600226

It shows that it is possible to perform a dynamic mechanical analysis inside a living zebrafish embryo without intervening with the embryonic development.

  1. Trap RBC in Living Mice Study: Zhong et al. (2013). Trapping red blood cells in living animals using Optical Tweezers. Nature Communications. 1768 (2013). https://doi.org/10.1038/ncomms2786

It uses the Optical Tweezers to trap and to manipulate red blood cells within subdermal capillaries in living mice.

  1. Measuring Flow and Drag Forces Imposed to Trapped RBC of Living Zebrafish Embryos Study: Harleep et al. (2017). Hemodynamic forces can be accurately measured in vivo with Optical Tweezers. Mol Bio Cell. 28(23): 3252–3260. 10.1091/mbc.E17-06-0382

It uses the Optical Tweezers to measure flow profiles and drag forces imposed to trapped red blood cells of living zebrafish embryos. This aims to calibrate the trap stiffness properly in vivo.

  1. Probing Cell Mechanics in Drosophila Embryo Study: Chardes et al. (2017). Probing Cell Mechanics with Bead-Free Optical Tweezers in the Drosophila Embryo. J Vis Exp. 2:141. 10.3791/57900

It uses the Optical Tweezers coupled to a light sheet microscope to apply forces on cell-cell contacts of the early Drosophila embryo, while imaging at speed of several frames per second.

 

Giant Unilamellar Vesicles (GUV)-based studies

Studying giant unilamellar vesicles (GUVs) with optical tweezers offers valuable insights into membrane biophysics, cell mechanics, and molecular interactions. GUVs are artificial, cell-sized vesicles composed of a single lipid bilayer, which makes them excellent model systems for investigating the properties and behavior of biological membranes in a controlled environment. Optical tweezers provide precise, non-invasive manipulation of GUVs, making them an ideal tool for studying these vesicles.

  1. Generating Membrane Nanotubes from Lipid Vesicles Study: Prévost et al. (2017). Pulling Membrane Nanotubes from Giant Unilamellar Vesicles. J. Vis. Exp. (130), e56086, doi:10.3791/56086. 10.3791/56086

It shows that Optical Tweezers can be used to generate lipid nanotubes by pulling on GUV.

  1. Generating Long Tubular Nanostructures Resembling Biological Membranes from GUV Study: Roux et al. (2005). Role of curvature and phase transition in lipid sorting and fission of membrane tubules. The EMBO Journal. 24(8):1537-1545. 10.1038/sj.emboj.7600631

It uses Optical Tweezers to generate lipid nanotubes by pulling on GUV.

  1. Characterization of membrane protein dynamics using GUV and SUV Study: Wang et al. (2021). Single-molecule manipulation of macromolecules on GUV or SUV membranes using Optical Tweezers. Biophys J. 120(24): 5454-5465, 10.1016/j.bpj.2021.11.2884

It uses Optical Tweezers to examine optical trapping and to probe the mechanical properties of two model membranes, namely GUV and SUV. The context is to study membrane protein dynamics.

  1. Stretching GUV Study: Solmaz et al. (2021). Optical stretching of giant unilamellar vesicles with an integrated dual-beam optical trap. Biomed Opt Express. 3(10): 2419-2427, 10.1364/BOE.3.002419

It uses Optical Tweezers to stretch GUV and to characterize the membrane response to a step stress.

  1. Sculpting and fusing biomimetic vesicle networks Study: Bolognesi et al. (2018). Sculpting and fusing biomimetic vesicle networks using Optical Tweezers. Nature Communications. 1882, https://doi.org/10.1038/s41467-018-04282-w

It uses Optical Tweezers to reconfigure and dismantle networks of cell-sized vesicles.

 

Measurement of Cellular Binding or Interaction Forces

Optical Tweezers are particularly useful for measuring cellular binding or interaction forces because they allow researchers to quantify the weak, dynamic forces involved in molecular and cellular interactions with high precision. By trapping and manipulating individual cells or biomolecules, Optical Tweezers can measure the forces required to form or break molecular bonds, such as those involved in receptor-ligand interactions, cell adhesion, or immune responses. This technique enables real-time observation of binding events and interaction dynamics, providing critical insights into cellular processes. Importantly, because Optical Tweezers are non-invasive, they preserve cell viability and function, allowing for the study of living cells under near-physiological conditions.

Here are several Optical Tweezers applications in measurement of cellular interaction forces:

  1. Human Bone Cells and Implant Surfaces Study: Andersson et al. (2007). Using Optical Tweezers for measuring the interaction forces between human bone cells and implant surfaces: System design and force calibration. Sci. Instrum. 78, 074302. https://doi.org/10.1063/1.2752606.

It uses Optical Tweezers to explore the interaction and attachment of human bone cells to various types of medical implant materials.

  1. Motility Forces of Isolated Chromosomes Study: Khatibzadeh et al (2014). Determination of motility forces on isolated chromosomes with laser tweezers. Sci Rep, 4:6866. 10.1038/srep06866

It uses Optical Tweezers to determine quantitatively the chromosome motility forces during cell divisions.

  1. Ligand – Receptor Binding in Living Cells Study: Riesenberg et al (2020). Probing Ligand-Receptor Interaction in Living Cells Using Force Measurements with Optical Tweezers. Front. Bioeng. Biotechnol. Vol.8. https://doi.org/10.3389/fbioe.2020.598459  

It uses Optical Tweezers to probe the binding kinetics of COOh-terminus of a toxin and claudin expressing MCF-7 cells.

  1. Fibrinogen – Integrin Binding in Living Cells Study: Litvinov et al (2002). Binding strength and activation state of single fibrinogen-integrin pairs on living cells. PNAS. 99(11)7426-7431. https://doi.org/10.1073/pnas.11219499

It uses Optical Tweezers to determine the rupture forces required to separate single ligand-receptor pairs.

  1. Determining position-dependent linkages of multiple proteins. Study: Nishizaka et al (2000). Position-dependent linkages of fibronectin– integrin–cytoskeleton. PNAS. 97(2)692-697. https://doi.org/10.1073/pnas.97.2.692

It uses Optical Tweezers to examine the position dependence of fibronectin bead binding on NIH-3T3 cells.

 

Mechanical Characterization

Optical Tweezers are highly useful for mechanical characterization because they enable precise manipulation and measurement of microscopic particles without physical contact. By using a focused laser beam to trap and move small objects such as cells, biomolecules, or nanoparticles, Optical Tweezers can exert finely controlled forces in the pico- to nanonewton range. This allows researchers to study the mechanical properties of materials, like stiffness, elasticity, or molecular interactions, with exceptional precision. Additionally, their non-invasive nature ensures minimal damage to delicate samples, making them ideal for biological systems and soft matter, where conventional tools may be too disruptive.

Here are several Optical Tweezers applications in mechanical characterization of single cells:

  1. Leukemia Cells Study: Zhou et al (2014). Accurate Measurement of Stiffness and Leukemia Cells and Leukocytes Using an Optical Trap by a Rate-Jump Method. RSC Advance, 4, 8453-8460. https://doi.org/10.1039/C3RA45835K

It shows how Optical Tweezers system can be used to measure the stiffness of non-adherent K562 myelogenous leukemia cells, which are the softest types of cells

  1. Cytoplasm Stiffness in Plant Cells Study: van der Honing et al (2010). Actin and myosin regulate cytoplasm stiffness in plant cells: a study using Optical Tweezers. New Phytol. 185(1):90-102. 1111/j.1469-8137.2009.03017.x

It uses Optical Tweezers to create cytoplasmic protrusions resembling cytoplasmic strands and to determine whether stiffness is an actin-related property of plant cytoplasm.

  1. Drug-treated Jurkat Cells Study: Khakshour et al (2010). Mechanical characterization of ART-treated Jurkat cells using Optical Tweezers. Annu Int Conf IEEE Eng Med Biol Soc. 6806-9. 1109/EMBC.2014.6945191

It uses Optical Tweezers to characterize the mechanical properties of Jurkat cells exposed to artesunate (ART) a chemotherapy.

  1. Cancer Cells under Hypoxia Study: Khakshour et al (2017). Retinoblastoma protein (Rb) links hypoxia to altered mechanical properties in cancer cells as measured by an Optical Tweezers. Sci Rep. 7(1):7833. 1038/s41598-017-07947-6  

It uses Optical Tweezers to characterize the biophysical properties of human prostate cancer cells that occur in response to loss of the retinoblastoma protein (Rb) under hypoxic stress.

  1. Red Blood Cells Elasticity in response to Antimalarials Study: Dorta et al (2017). Optical Tweezers to measure the elasticity of red blood cells: a tool to study the erythrocyte response to antimalarials. Malar. Vol 2. https://doi.org/10.3389/fmala.2024.1362644

It uses Optical Tweezers to compare the membrane stiffness of uninfected vs infected red blood cells. Additionally, the effect of antimalarial drugs to uninfected red blood cells.

  1. The Stiffness of Alginate-Gelatin Hydrogel Study: Ling et al (2022). A Novel Step-T-Junction Microchannel for the Cell Encapsulation in Monodisperse Alginate-Gelatin Microspheres of Varying Mechanical Properties at High Throughput. 12(8):659. 10.3390/bios12080659

It uses Optical Tweezers to measure the stiffness of alginate-gelatin hydrogel.

  1. Membrane Cell Tension Study: Kreysing et al (2022). Effective cell membrane tension is independent of polyacrylamide substrate stiffness. PNAS Nexus. 2(1):pgac299. 1093/pnasnexus/pgac299

It uses Optical Tweezers to measure the effective membrane tension of neurons and fibroblasts cultured on substrate with varying rigidities.

  1. Rheological Properties of Fibroblasts, Neurons, and Astrocytes Study: Ayala et al (2016). Rheological properties of cells measured by Optical Tweezers. BMC Biophysics. 9:5. https://doi.org/10.1186/s13628-016-0031-4

It uses Optical Tweezers to determine the storage and loss moduli of cells membrane cortex complex.

  1. Viscosity of out-of-equilibrium System Study: Madsen et al (2021). Ultrafast viscosity measurement with ballistic Optical Tweezers. Nature Photonics. 15, 386-392. https://doi.org/10.1038/s41566-021-00798-8

It uses Optical Tweezers with measurement speed reaching 20 microseconds to measure and translate viscosity from a static averaged property to one that may be dynamically tracked on the timescales of active dynamics.

  1. Ex Vivo Generated Red Blood Cells Study: Bernecker et al (2021). Biomechanics of Ex Vivo-Generated Red Blood Cells Investigated by Optical Tweezers and Digital Holographic Microscopy. 10(3):552. 10.3390/cells10030552

It uses Optical Tweezers to measure deformation and elasticity of single cells aimed to investigate membrane properties dependent on membrane lipid content.

 

Molecular Motor Studies

Molecular motors, such as myosin, kinesin, and dynein, are proteins that convert chemical energy into mechanical work, driving processes like muscle contraction, intracellular transport, and cell division. To understand how these motors function at the molecular level, researchers need a tool that can exert controlled forces on microscopic particles while observing their movement in real-time — this is where Optical Tweezers excel.

Here are several Optical Tweezers applications in studying molecular motors:

  1. Microtubule Translocation by Single Kinesin Study: Kuo and Sheetz (1993). Force of single kinesin molecules measured with Optical Tweezers. 260(5105):232-4. 10.1126/science.8469975

It uses Optical Tweezers to measure necessary forces by single kinesin molecules to translocate microtubule

  1. Kinetochore – Microtubule Interaction Study: Muir et al (2023). Structural mechanism of outer kinetochore Dam1-Ndc80 complex assembly on microtubules. Vol 382, No. 6675 pp 1184-1190. DOI: 10.1126/science.adj8736

It uses Optical Tweezers generate rupture force between the microtubule and the kinetochore structure.

  1. Single Kinesin Moving a Bead Study: Block et al (2007). Bead movement by single kinesin molecules studied with Optical Tweezers. Nature. 348(6299):348-52. 1038/348348a0

It uses Optical Tweezers to trap beads coated with kinesin protein and to expose them to microtubules.

  1. F-Actin and Titin Interaction Study: Bianco et al (2007). Interaction Forces between F-Actin and Titin PEVK Domain with Optical Tweezers. Biophysical Journal. 93, Issue 6, P2102-2109. https://doi.org/10.1529/biophysj.107.106153

It uses Optical Tweezers to measure necessary forces to dissociate F-actin from individual molecules of recombinant PEVK fragments.

  1. Single Myosin Molecule – Single Suspended F-actin Interaction Study: Finer et al (2007). Single Myosin Molecule Mechanics: Piconewton Forces and Nanometre Steps. Nature. 368, 113-119. https://doi.org/10.1038/368113a0

It uses Optical Tweezers to bring a single myosin molecule in contact with single F-actin filament. The magnitude of single forces and displacements are in-line with the prediction using the conventional swinging-crossbridge model of muscle contraction.

  1. Myosin V stepping on F-actin Study: Capello et al (2007). Myosin V Stepping Mechanism. PNAs. 104(39)15328 – 15333. https://doi.org/10.1073/pnas.0706653104  

It uses Optical Tweezers to bring myosin-coated bead in contact with the F-actin filaments.

  1. Determining the Working Stroke of Rabbit Heavy Meromyosin Study: Veigl et al (2007). The Stiffness of Rabbit Skeletal Actomyosin Cross-Bridges Determined with an Optical Tweezers Transducer. Journ. Vol. 75, Issue 3, 1424-1438. https://doi.org/10.1016/S0006-3495(98)74061-5

It uses Optical Tweezers to measure the cyclical interaction of myosin with actin known as the “working stroke”.

  1. Dynein – Microtubule Interaction Study: Brenner et al (2007). Force production of human cytoplasmic dynein is limited by its processivity. Adv. Vol. 6, No 15. DOI: 10.1126/sciadv.aaz4295

It uses Optical Tweezers to reveal the stall force of dynein molecule is about 2 pN.

  1. Talin – Integrin Bond Study: Bodescu et al (2007). Kindlin stabilizes the talin·integrin bond under mechanical load by generating an ideal bond. 120(26):e2218116120. 10.1073/pnas.2218116120

It uses Optical Tweezers to investigate mechanical stability of talin-integrin bond in the presence and absence of kindlin.

  1. Single Fibrinogen – Integrin Pair Bond Study: Litvinov et al (2002). Binding strength and activation state of single fibrinogen-integrin pairs on living cells. 99 (11) 7426-7431. https://doi.org/10.1073/pnas.112194999

It uses Optical Tweezers to determine the rupture forces required to separate single ligand-receptor pair either purified proteins or intact living cells.

 

DNA/RNA Interaction Forces

Optical tweezers are highly valuable for studying DNA or RNA interaction forces because they enable precise manipulation of these delicate molecules to measure the forces involved in processes such as folding, unfolding, and binding with proteins or other nucleic acids. By trapping and stretching individual DNA or RNA strands, researchers can directly observe mechanical responses to applied forces, providing insights into their structural stability and interactions with enzymes like polymerases or helicases. This technique allows for real-time, single-molecule measurements of molecular interactions, which is critical for understanding the mechanics of transcription, replication, and gene regulation. The ability to perform these studies without damaging the nucleic acids ensures accurate, biologically relevant results.

Here are several Optical Tweezers applications in studying DNA interaction forces:

  1. Unzipping DNA Study: Bockelmann et al (2002). Unzipping DNA with Optical Tweezers: High Sequence Sensitivity and Force Flips. Journ. Vol. 82, Issue 3, P1537-1553. 10.1016/S0006-3495(02)75506-9

It uses Optical Tweezers to measure the force corresponding to the DNA (several thousand basepairs) unzipping at low velocity

  1. Stretching DNA Study: Wang et al (1997). Strecthing DNA with Optical Tweezers. Biophys Mar; 72(3): 1335–1346. https://doi.org/10.1016%2FS0006-3495(97)78780-0

It uses Optical Tweezers to stretch DNA, while the position of the bead was recorded at nanometer scale resolution.

  1. Coiled coil force sensor coupled to DNA handle Study: Ren et al (2023). Force redistribution in clathrin-mediated endocytosis revealed by coiled-coil force sensor. Sci Adv. 9(41):eadi1535. 1126/sciadv.adi1535

It uses Optical Tweezers combined with in vivo coiled-coil force sensor to reveal the force redistribution during endocytosis.

  1. Using DNA as Standard for Length and Force Measurements Study: Rickgauer et al (2006). DNA as a Metrology Standard for Length and Force Measurements with Optical Tweezers. Vol. 91, Issue 11, 4253-4257. https://doi.org/10.1529/biophysj.106.089524

It uses DNA molecules as metrology standards for length and force measurements in Optical Tweezers.

  1. DNA-protein-DNA Force Extension, Manipulation, and Visualization Study: Brouwer et al (2017). Human RAD52 Captures and Holds DNA Strands, Increases DNA Flexibility, and Prevents Melting of Duplex DNA: Implications for DNA Recombination. Vol. 18, Issue 12, 2845-2853. https://doi.org/10.1016/j.celrep.2017.02.068

It uses multiple optical trap configurations to trap beads and catch DNA molecules in between.

  1. Observing Mechano-Chemical Cycles of DNA Packaging by φ29 Motor with Base Pair Resolution Study: Chistol et al (2017). High Degree of Coordination and Division of Labor among Subunits in a Homomeric Ring ATPase. Vol. 151, Issue 5, P1017-1028. https://doi.org/10.1016/j.cell.2012.10.031

It uses Optical Tweezers to pull and perform the equilibrium experiments to probe structural dynamics and conformational changes during genome packaging.

  1. Observing How Biomolecular Condensation Physically Prevents DNA End Disjunction Study: Chappidi et al (2024). PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends. Vol. 187, 945-961. https://doi.org/10.1016/j.cell.2024.01.015

It uses Optical Tweezers to investigate the recruitment of PARP1 protein to DNA double stranded breaks.

  1. Studying RNA-Protein Interactions in Translation Regulation Study: Pekarek et al (2022). Optical Tweezers to Study RNA-Protein Interactions in Translation Regulation. J Vis Exp. 12:180. https://doi.org/10.3791/62589

It uses single-molecule-fluorescence-coupled Optical Tweezers to explore the conformational and thermodynamic landscape of RNA-protein complexes at a high resolution.

  1. Observing RNA Force Unfolding Kinetics  Study: Wen et al (2007). Force Unfolding Kinetics of RNA Using Optical Tweezers. I. Effects of Experimental Variables on Measured Results. Journ. Vol. 92, Issue 9 P2996-3009. https://doi.org/10.1529/biophysj.106.094052

It uses Optical Tweezers to investigate RNA folding/unfolding kinetics.

  1. Studying the Transcription by Eukaryotic RNA Polymerases Study: Lisica and Grill (2017). Optical Tweezers Studies of Transcription by Eukaryotic RNA Polymerases. Biomolecular Concepts. Vol. 8, Issue 1. https://doi.org/10.1515/bmc-2016-0028

It uses Optical Tweezers to study transcription dynamics.

 

Laser Raman Tweezers

Combining Optical Tweezers with Raman spectroscopy is highly useful because it enables simultaneous manipulation and molecular analysis of small particles or biological molecules with high precision.

Here are several Laser Raman Tweezers applications:

  1. Comparing the Deformability of Human vs Camel Red Blood Cell Study: Pesen et al (2023). Comparison of the human’s and camel’s red blood cells deformability by Optical Tweezers and Raman Spectroscopy. Biochemistry and Biophysics Reports, Volume 35. https://doi.org/10.1016/j.bbrep.2023.101490

It uses Optical Tweezers to observe the mechanochemical differences between human and camel red blood cells.

  1. Automated Raman-based Live Cell Sorter Study: Lee et al (2023). An automated Raman-based platform for the sorting of live cells by functional properties. Nature Microbiology, 4, 1035-1048. https://doi.org/10.1038/s41564-019-0394-9

It uses an optofluidic platform combining microfluidics, Optical Tweezers, and Raman microspectroscopy to automatically sort the stable-isotope-probing-labelled microbial cells.

  1. Automated Raman-based Live Cell Sorter to Identify Bacteria in the Gut Microbiota Study: Riva et al (2023). Identification of inulin-responsive bacteria in the gut microbiota via multi-modal activity-based sorting. Nature Communication, 14, 8210. https://doi.org/10.1038/s41467-023-43448-z

It uses a multi-modal activity-based sorting including Optical Tweezers to identify bacteria in the gut microbiota.

  1. Identifying microplastics and nanoplastics in seawater Study: Gillibert et al (2019). Raman Tweezers for Small Microplastics and Nanoplastics Identification in Seawater. Sci. Technol. Vol. 53/Issue 15, 9003-9013. https://doi.org/10.1021/acs.est.9b03105

It uses combined Optical Tweezers and Raman Spectroscopy to chemically identify sub-20 microns down to the 50 nm range plastics.

  1. Space Application: Investigation of Dust Grains Study: Magazzu et al (2023). Investigation of Dust Grains by Optical Tweezers for Space Applications. The Astrophysical Journal. 942 11. 3847/1538-4357/ac9a45

It uses combined Optical Tweezers and Raman Spectroscopy to manipulate individual dust particles in a water solution and to characterize their response to mechanical effects of light and to determine their mineral composition.

 

Biosensor or Bio-tool assays

Optical tweezers are extremely useful for designing biosensor and bio tools assays because they enable precise manipulation of individual molecules or particles, facilitating the development of highly sensitive and specific detection methods. By measuring forces at the nanoscale, optical tweezers allow researchers to probe biomolecular interactions with exceptional accuracy, helping to fine-tune biosensors for detecting pathogens, toxins, or other target molecules. This technique is particularly valuable for characterizing binding affinities and kinetics in real-time, which is crucial for optimizing the performance of biosensor systems. Moreover, their non-invasive nature allows for the study of biological systems under near-physiological conditions, improving the relevance and reliability of the assays.

Here are several applications of Optical Tweezers methods integrated to biosensor or bio-tool assay:

  1. Single-Cell Isolation Following Time Lapse Imaging (SIFT) Study: Luro et al (2020). Isolating live cells after high-throughput, long-term, time-lapse microscopy. Methods, 17(1):93-100. https://doi.org/10.1038/s41592-019-0620-7

It uses the combination of fluorescence imaging, microfluidics, and Optical Tweezers to image and track individual bacteria for tens of consecutive generations under tightly controlled growth conditions, cells of interest are isolated and propagated for downstream analysis, free of contamination and without genetic and physiological perturbations.

  1. Neutrophil Microrobot Study: Liu et al (2022). Optically Manipulated Neutrophils as Native Microcrafts In Vivo. ACS Central Science, Vol8/Issue7, 2374-7943. https://doi.org/10.1021/acscentsci.2c00468

An optically manipulated neutrophil microcraft was developed through the organic integration of the innate immunologic function of neutrophils and intelligent optical manipulation.

  1. Spermatozoa Isolation from Mixed Forensic Samples Study: Auka et al (2019). Optical Tweezers as an effective tool for spermatozoa isolation from mixed forensic samples. PLoS One. 2019 Feb 7;14(2):e0211810. 1371/journal.pone.0211810

It uses Optical Tweezers to isolate sperm cells from a mixture of sperm and vaginal epithelial cells.

  1. Auto-focusing of nuclei for time lapse experiments on single cells Study: Eriksson et al (2009). Automated focusing of nuclei for time lapse experiments on single cells using holographic Optical Tweezers. Optics Express. Vol. 17, Issue 7. Page 5585-5594. https://doi.org/10.1364/OE.17.005585

It uses Optical Tweezers to optimize the axial position of single cells to eliminate the need of z-stacking, therefore reduces photobleaching and improves the time resolution in time lapse imaging.

  1. Tele-Robotic Platform Study: Gerena et al (2009). Tele–Robotic Platform for Dexterous Optical Single-Cell Manipulation. Micromachines (Basel). 10(10): 677. 3390/mi10100677

It uses Optical Tweezers to generate an optical-robot with a fork-end effector to dexterously manipulate a single cell.

 

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