Many cellular processes are performed by highly specialized and evolved entities that function as molecular machines. Some of these protein machines operate cyclically converting chemical energy into mechanical work through the generation of force or torque and displacement. These machines are referred to as “molecular motors”. I will give examples of several molecular motors in the cell, as well as their classification in terms of their mode of operation. The mechanical paradigm in biology is not new; as I will show, these ideas have been around since the XVII century, but our understanding of their operation has increased enormously through the use of single molecule manipulation methods and of modern biophysical techniques such as optical tweezers. I will describe some of our recent results in the study of the DNA packaging motor of bacteriophage Phi29, including its impressive thermodynamic efficiency. This is a feature that is common to many motors of biological origin. I will then speculate about the possible origin of this energetic efficiency based on recent results about energy dissipation. I will end by describing the impressive coordination among the different parts of the packaging motor using high-spatial resolution optical tweezers.

The mechanosensitive nature of the TCR-pMHC interaction in T cells has been studied via optical tweezer experiments. From these studies, populations of force responsive T cells (digital cells) that recover activation potential in sparse pMHC environments have been discovered. Through a series of optical tweezer experiments, the distinctions between the digital population and their counterpart T cells will be examined. These include triggering ability at varying pMHC copy numbers and the stiffness changes in the T cell membrane as measured through microrheology.

Optical tweezers have become ubiquitous tools in science with use in disciplines ranging from biology to physics, chemistry, and material sciences with thousands of users around the world and a continuously growing number of applications. Here we show how a specially designed instrument, called miniTweezers2.0, can be made both highly versatile and user friendly. We demonstrate the system on three different experiments, which thanks to the close integration of the various parts of the tweezers into a single software are performed largely autonomously. The first experiment involves DNA stretching, a fundamental single molecule force spectroscopy experiment. The second experiment involved the stretching of red blood cells, which can be used to gauge the membrane stiffness of the cells. Lastly, we investigate the interaction between core-shell particles in various environments. Showing how the soft polymer layer extends, or contracts depending on pH and salinity. Our work show potential of automated and versatile optical tweezers systems in advancing our understanding of nano and micro-scale systems.

Accurate chromosome segregation during cell division relies on coordinated actions of microtubule-based motor proteins in the mitotic spindle. Kinesin-14 motors play vital roles in spindle assembly and maintenance by crosslinking antiparallel MTs at the spindle midzone and anchoring spindle MTs’ minus ends at the poles. We investigate the force generation and motility of the kinesin-14 motors HSET and KlpA, revealing that both motors function as non-processive motors under load, producing single ~25 nm power strokes per MT encounter. Each homodimeric motor generates forces of ~0.5 pN, but when assembled in teams, they cooperate to generate forces of 1 pN or more. Importantly, cooperative activity among multiple motors leads to increased MT-sliding velocities. Our findings quantitatively elucidate the structure-function relationship of kinesin-14 motors and underscore the significance of cooperative behavior in their cellular functions.

To gain a better understanding of material properties of chromatin and successfully link them to chromatin organization and functions such as transcription, we develop novel methods to actively manipulate a genomic locus inside the nucleus of a living human cell. By targeting iron-containing nanoparticles to a specific genomic locus and applying a controlled magnetic field, we were able to physically move chromatin through nuclear space for the first time. Exertion of near-picoNewton forces led to displacements over microns within minutes. We observe partially reversible stretching of chromatin highlighting its’ viscoelastic nature. We could accurately recapitulate the observed behavior with a Rouse model that included only a weak obstructive effect of the surrounding chromatin and nucleoplasmic material. This challenges the view that interphase chromatin is a gel-like material.

Hypertrophic cardiomyopathy (HCM) is a symptomatic affliction due to mutations in cardiac contractile proteins. We compared a highly penetrant mutation in cardiac myosin, M493I, with wild type (WT) using an advanced optical trap assay capable of quantifying kinetic rates including actomyosin re-attachment. Kinetic changes in both the actomyosin attachment and detachment rates suggest that the equilibrium between a conformation termed the Interacting Head Motif (IHM) and freely available myosin heads is disturbed in M493I. This type of disruption has been hypothesized to lead to the toxic hypertrophy observed in patients.

Extracellular vesicles and particles (EVPs), once considered as a means for cells to expel wastes, are now recognized as vital mediators of cell-to-cell communication. They transport essential molecules like mRNA, miRNA, proteins, and lipids, facilitating both local and long-distance signaling. However, their diverse origins and sizes pose a challenge for understanding their roles in health and disease. Traditional optical tweezers face limitations due to the small size of EVPs and the diffraction limit of light. In this discussion, I will introduce innovative optical nanotweezers utilizing plasmonic and dielectric nanoantennas to rapidly trap and analyze single EVPs, overcoming previous obstacles. These novel non-invasive light-based tools with multifunctional capabilities are expected to open new horizons by enabling to address fundamental questions in EVP biology and drive translational applications in novel therapeutics, as well as environmental monitoring.

For over a decade, our group has been trapping and analyzing single proteins using a double nanohole in a metal film. Our recent investigations have sought to improve the nanofabrication, including bottom-up mass-fabrication and a new fiber-based platform for microwell format investigation. We have also been developing approaches to modify the environment around a single trapped protein, for example, by integrating microfluidics and allowing for varying the background temperature. This allows for measuring properties like the optical size, hydrodynamic size, charge and thermophoretic properties a trapped protein. These new capabilities will be presented in this work.

We present a method for trapping nanoscale biological particles without causing photothermal heating, using all-dielectric optical nanotweezers. This technique focuses the accessible electromagnetic energy to as small as 30 nm, enabling the trapping and imaging of nanosized biological specimens including extracellular vesicles and lipoproteins with minimal temperature increase. This advancement offers new opportunities in single molecule analysis and opens the door to understanding the diversity of extracellular particles.

Plasmonic apertures concentrate optical fields, enhancing the gradient force for precise trapping of nanoscale entities. Traditionally, design relied on intuition and simulations. We instead present a novel approach using topology optimization and adjoint sensitivity analysis. Our computational algorithm inversely designs plasmonic nanoapertures. Surprisingly, the algorithm produces an aperture reminiscent of the double nanohole, a structure that has been adopted by many groups. Our algorithm produces outer structures that surround the aperture and enhance the electric field intensity, increasing trapping potential by ~4.97 times. Compared to representative studies, our design achieves ~1.95 and ~27.9 times greater trapping potential than algorithm-designed and forward-designed nanotweezers, respectively. This work establishes topology optimization as an effective method for high-performance plasmonic nanotweezer design.

Our optical positioning and linking (OPAL) platform is based on optical tweezers and can assemble sub-micron heterogeneous materials in three dimensions (3D). OPAL is fully automated and can position hundreds of particles according to a set of desired predetermined coordinates. After positioning, particles are permanently liked together via biotin-avidin chemistry. We present how the fabrication speed, positional accuracy, and error rate depend on process parameters. The rapid prototyping of metamaterials and nanostructured optical chemical sensors will be discussed, as well as novel computational design approaches for these devices based on the discrete dipole approximation.

Optical skyrmions, that is particle-like optical fields with topologically protected polarization textures (such as Néel-, Bloch-, and anti-skyrmions), have been recently demonstrated. Optical skyrmions have been utilized in advanced applications such as free-space communications under turbulent conditions, and super-resolution microscopy with sub-wavelength spatial resolution. Optical skyrmions are also potentially expected to offer new fundamental physics via exotic light matter interactions, however, they are still in their infancy as a research topic, and there are few reports of the interaction between optical skyrmions and materials. We herein report on the first demonstration of direct imprint of the topologically protected polarization textures of optical Néel-, Bloch-, and anti-skyrmions onto a material, as a surface relief in azo-polymers. This demonstration strongly evidences the capacity of the optical skyrmions for new approaches to materials manipulation.

We use an optical positioning and linking (OPAL) platform based on optical tweezers to fabricate a grating coupler on a microtoroid-shaped optical resonator for highly efficient coupling of light into the resonator, which acts as a chemical sensor. Light is coupled into and out of the microtoroid through a grating fabricated from 0.5 µm polystyrene particles on the rim of the microtoroid, which acts as a fiber-free coupler. Unlike a tapered fiber coupler, this particle grating is highly robust and not susceptible to mechanical and vibrational noise, paving the way for field-portable sensing devices.

Brain cells are complex and delicate materials with unique physical properties that can be influenced by physical stress. Recent studies have shown that physical stress affects the biological response of molecules inside living cells. We have been developing a single-objective light-sheet microscope and optical manipulation tools to investigate the dynamic properties of living brain cells. This integration allows us to observe 3D biological processes with high precision while enabling the manipulation and characterization of individual cells and microcompartments. In this presentation, I will explain the operating principles of multimodal optical force microscopy, share preliminary results, and discuss future applications.

Light-powered microrobotic swarms, excelling in manipulation efficiency and motion pattern customization, are pivotal for micro-fabrication and biomedical applications. Herein, we introduce an integrated platform capable of autonomously transporting light-powered microrobotic swarms over long distances within complex environments. The embedded real-time feedback control algorithm ensures swarm integrity and facilitates the adept navigation around unpredictable obstacles. The successful operation of both trapping- and nudging-based microrobots prove the versatile applicability of our platform.

A rigid body can have 6 degrees of freedom, namely the three translational degrees of freedom and further, the three rotational degrees of freedom. Of these, the translational degrees have been well explored in optical tweezers community. However, only the in-plane rotational degree of freedom which we call the yaw motion in the nomenclature of the airlines, has been explored. The pitch and roll degrees are only beginning to be explored recently. In this talk, I will exhibit 4 ways of generating pitch rotation using the optical tweezers. I will also show you one way of detection of pitch rotation at high resolution using birefringent particles. Further, I will also discuss some applications of this pitch rotation in soft matter systems and biology, particularly usage to detect cell membrane fluctuations and rheology in the cell interior.

Ballistic measurements using rotational optical tweezers determine the viscosity of fluids much faster than with conventional methods. They have the unique advantage of being calibration-free and using low laser powers that limit negative heating effects. This makes the technique ideal for performing ultrafast dynamic viscosity measurements in biological systems and will provide useful insight into the behaviour of dynamic environments.

Optics researchers have seen huge developments in the understanding, control, and measurement of optical angular momentum in the 21st century. These insights have generally been enabled by advances in semi-conductor technology in both experiments and computation. I will cover three areas of optical angular momentum transfer that was enabled by these developments: spin—orbit coupling, beam shaping, and materials design. Recent technological advancements have enabled investigations of optical angular momentum and activity across a wide range of size scales. We have a good understanding of the optical elements through careful modelling of both the light that reaches objects and the scattering they cause. Structuring light enhances control of optical angular momentum transfer to matter, for example, to allow transfer of transverse angular momentum to wavelength sized particles. This approach can be generalised to optimise reflection, anisotropy, and absorption to enable control and measurement of matter. This in turn provides the impetus to create new devices for the same. I will cover previously published and new research of informed design of light fields and particles.

Self-propelled particles are becoming crucial components for various applications such as targeted drug delivery systems, active rheometry and powering microactuators for lab-on-chip devices among others. However, due to its size and the nature of the suspending medium, Brownian motion overcomes self-propulsion at some temporal ranges. Thus, one of the major challenges in autonomous operation is to overcome random fluctuations. In this work, we show a strategy to manipulate half metal-coated Janus particles using optical vortex beam. We observed that the Janus particles were confined and moves persistently along the ring trap. Angular speed measurements show a linear increase at increasing laser powers. Furthermore, we found that the orientation vector of the Janus particle aligns with the direction of the tangential driving. Our findings leads to new way of controlling self-propelled particles without the use of complex techniques such as feedback-loops.

Microengines have shown promise for a variety of applications in nanotechnology, from microfluidics to nanomedicine and targeted drug delivery. However, their precise control over their dynamics is still challenging. We introduce a micro engine that exploits both optical and thermal effects to achieve a high degree of controllability. We find that a gold-silica Janus particle illuminated by a high focused laser beam can be confined at the stationary point where the optical and thermal forces balance. By using circularly polarized light the symmetry between these forces can be broken by transferring angular momentum to the particle, resulting in a tangential force that induces an orbital motion of the particle. We can simultaneously control the velocity and direction of rotation of the particle, changing the ellipticity of the incoming light beam while tuning the radius of the orbit with laser power. We validate our results using a geometrical optics model that incorporates optical force, the absorption of optical power, and the resulting heating of the particle.

Optical diffraction tomography (ODT) is a valuable imaging technique in biomedicine, particularly for live cell and tissue studies, offering insights into cellular structures via refractive index assessment. However, traditional methods face limitations in scanning ranges, affecting resolution and imaging completeness. To address this, a compact multi-core fiber-optic system enables precise cell rotation within microfluidic chips, enhancing tomography resolution. Introducing an AI-driven reconstruction workflow promises automation and efficiency. Validation through phantom and cancer cell reconstructions showcases performance. Yet, ODT is hindered by weak scattering sample requirements, limiting its applicability to shallow single cells. A novel algorithm addresses this for thicker samples like C. Elegans, albeit with spatial resolution constraints. Combining this algorithm with the cell rotation system could revolutionize applications in flow cytometry and acoustic rotation tomography.

Optical levitation in ultra-high vacuum (UHV) and cryogenic environments provides a platform potentially capable of providing quantum coherences of tens to hundreds of milliseconds for objects such as silica nano-spheres which are much more massive than atoms and molecules. Demonstration of matter-wave interference with optically levitated nanospheres has the potential to extend the current limit on matter-wave interference by three to four orders of magnitude, pushing the experimental limits on matter-wave duality. This would provide pathways towards the realization of gravity-induced entanglement experiments, tests of decoherence and wave function collapse models. To preserve a coherence time of approximately 200ms, experimental challenges such as near motional ground state cooling pressures below 10−13mbar, internal temperatures below 100K, and relative position stability on the order of tens of nanometers must be overcome. This apparatus additionally allows for precision measurements of short-range forces to test Newtonian gravity at sub-micron scales, the Casimir Polder force, matter neutrality, and other fundamental forces.

We describe the characterization of single nanoparticles based on the measurement of their rotational and oscillatory motion when optically levitated within vacuum. Using colloidally grown yttrium lithium fluoride nanocrystals of different sizes, trapped in a single-beam optical tweezer, we demonstrate the utility of this method which is in good agreement with simulations of the dynamics. Size differences as small as a few nanometers could be resolved using this technique offering a new optical spectroscopic tool for non-contact characterization of single nanoparticles in the absence of a substrate

We describe the creation of an optical centrifuge for nanorotors formed by anisotropic nanoparticles levitated within an optical tweezer for the study of non-classical rotational motion. We also report on the experimental realization of the centrifuge enabled by a fast in-line polarization controller. This approach to the creation of well-defined rotational velocities is also compared to rapid switching between linear and elliptically polarized fields using the same polarization controller.

In optical levitation, a focused, vertically aligned laser beam is used to trap micrometer sized where the photon pressure from the light is balancing gravity. I will in this work review the field by presenting a number of different experiments. I will show how the Foerster Resonance Energy Transfer (FRET) mechanism can be used to track the dynamics of two coalescing glycerol droplets. Second, I will show the directional Mie spectrum of evaporating water droplets arrange in consecutive Fano Combs. This observation is explained by a quantum analogy where the droplet can be seen as an "optical atom" with angular momentum, tunneling, and excited states. Third, I will show how we have used optical levitation to create a single droplet version of Millikan's experiment where the effects of a single electron removal can be observed by the naked eye and measured with a ruler. Finally, I will present our ongoing efforts to trap nanometer sized particles in vacuum and a method to levitate metallic particles.

Optical levitation of dielectric objects in vacuum provides a unique optomechanical platform due to versatile optical control of potentials and good isolation from the environment. Recently, tunable and nonreciprocal optical interactions have been measured between two nanoparticles, levitated in two distinct optical tweezers, with single-site readout of particle motion. I will present our experimental platform for tweezer arrays of nanoparticles, and show our recent results on non-Hermitian collective dynamics of two nonreciprocally interacting nanoparticles. We also observe a mechanical lasing transition once a threshold coupling rate is achieved, supported by our nonlinear theory model. Nonreciprocal interactions are expected to result in an even richer phase diagram of nonequilibrium dynamics for larger arrays of nanoparticles. This work paves the way towards upscaling this platform to such multiparticle arrays, in view of studying their nonequilibrium and collective mechanical behaviour in the quantum regime.

Optically levitated particles in high vacuum achieve excellent environmental decoupling making them ultrasensitive detectors of forces or accelerations. While many levitated optomechanics experiments employ spherical particles, for some applications non-spherical geometries offer advantages. For example, rod-shaped or dumbbell shaped particles have been demonstrated for torque and rotation sensing and plate-like and disc-like particles with a high aspect ratio offer the possibility of a high mass-frequency product and low photon recoil heating, making them well suited for detection of high-frequency accelerations. I will discuss recent work on trapping and cooling high-aspect ratio dielectric particles and our progress towards achieving optimal detection of their motion to improve the sensitivity, cooling, and quantum control in these systems. Finally, I will place these results into context of the levitated sensor detector (LSD) experiment being constructed which intends to search for high-frequency gravitational waves.

Precise rotation of biological cells plays a pivotal role in in-situ bio-imaging and bioengineering. Here, we propose an integrated platform that enables the rotation of various ellipsoidal cells along their major and minor axes via tailoring the laser patterns and corresponding optothermal fields. Label-free in-situ three-dimensional(3D) imaging of living cells is achieved by 3D reconstruction.

In the field of in vitro fertilisation (IVF), there is a need to understand how cell properties of the cumulus oocyte complex may be used to predict successful pregnancy and live birth rates post-IVF. Here we used optical tweezers for the first time to measure the viscosity of the cumulus cell matrix surrounding the oocyte (egg). This study aimed to determine whether the viscosity of the cumulus cell matrix – prior to fertilisation – is reflective of subsequent embryo developmental potential and indicative of pregnancy success. Measurements were performed using a 1µm diameter silica probe particle trapped by a focused 1064nm laser. We benchmarked the accuracy of the system by measuring the viscosity of glycerol with varying mass fractions. Viscosity measurements of the cumulus cell matrix were performed in isolation from both the cumulus cells and the oocyte. This showed that the viscosity of cumulus matrix was significantly higher when sampled from oocytes with a higher developmental potential (in vivo matured) compared to those of lower quality (in vitro matured).

Living cells are among the most complex systems studied from both biological and physical perspectives. While cell biology has made tremendous advances in understanding the molecular composition of cells, our understanding of the physical characteristics within cells is not as advanced. We use optical tweezer-based active and passive microrheology to characterize the intracellular viscoelasticity and active forces, revealing significant variability in physical properties among different cell types. Furthermore, to facilitate passive microrheology in active systems, we introduce a novel stochastic observable based on a three-point correlations function. We will discuss these innovative approaches and the underlying analysis, which paves the way for a deeper physical understanding of living materials through "feeling" the cells using optical forces.

How local nonlinear stresses propagate through soft matter systems remains an important open question. Here, I present a powerful approach–Optical Tweezers integrating Differential Dynamic Microscopy (OpTiDDM)–that simultaneously imposes local strains, measures resistive forces, and analyzes the motion of the surrounding polymers. By coupling optical tweezers with fluorescence microscopy, we are able to precisely map the time-dependent deformation fields arising from local nonlinear straining in biopolymer networks and complex fluids. Specifically, we measure the stresses imposed in the fluids by local optically-driven strains, and simultaneously image labeled biopolymers surrounding the strain site. Using DDM, we characterize the macromolecular dynamics and deformation as a function of strain rate and distance from the applied strain. With its robust suite of capabilities, as well as its modular and adaptable design, we anticipate broad interdisciplinary use of OpTiDDM to elucidate non-trivial phenomena that dictate and are impacted by the propagation of local stresses through a system–critically important to commercial materials applications and cell mechanics alike.

Particle uptake is of huge interest in pharmacology and medicine, but a user-controlled uptake of particles into GUVs has been technically demanding. Here, we indent the membrane of differently composed GUVs with optically trapped particles until particle uptake. By continuous 1MHz back-focal-plane interferometric tracking and autocorrelating the particle’s positions within 30µs delays for different indentations, the fluctuations’ amplitude, the damping, the mean forces, and the energy profiles were obtained. The study demonstrates that soft matter can interact completely differently on different temporal and spatial frequency modes, which are excited by the environmental thermal noise.

Integrated optofluidic nanopore sensor technologies have enabled label-free quantification of molecular biomarkers by digital detection of target biomolecules with the electrical translocation signal created during passage through a nanoscale opening. The approach utilizes planar waveguide-based optical trapping combined with a customized microfluidic channel geometry for million-fold target concentration enhancement underneath a nanopore. The optofluidic device design is optimized for better optical trapping performance utilizing both gradient and scattering optical forces. Combined with a target-specific bioassay, this simple, direct, and highly sensitive detection method enables amplification-free and calibration-free biomarker quantification. Using this platform, we show viral load day progression of Zika and SARS-CoV-2 infections from different biofluids in primate models across the clinically relevant concentrations range (five orders) down to 10 aM –comparable to and sometimes improving upon qRT-PCR results. We also report the use of this integrated sensor for extracellular vesicle cargo monitoring from cerebral organoids grown in conditioned media.

When light, or electromagnetic radiation, impacts a surface, it generates a force known as radiation pressure. In this study, we explore the radiation pressure generated by a finite, structured light beams and how it differs from that of a plane wave at an identical frequency. A notable characteristic of structured beams, especially as they pass through their focal point, is the accumulation of an extra phase shift, unlike a plane wave traveling the same distance. This phenomenon, known as the Gouy phase, underpins the difference in radiation pressure that we observe. One case we focus on is for Laguerre-Gaussian modes, and we detail specific experimental approaches to quantify the variance in radiation pressure, which amounts to approximately 20fN/W for each unit of orbital angular momentum.

In this work we theoretically and experimentally study the the induction of electromagnetic forces in three-dimensional magnetic photonic glass when light impinges normally onto an assembly of SiO2 spheres known as artificial opals infiltrated with Fe3O4 nanoparticles.

Often beams, such as optical bottle beams (OBBs), possess rotational asymmetry, or other defects in the beam's intensity distribution. These beams are often due to nodal surfaces formed by the discontinuous phases which are typically necessary for the beam's unique intensity distribution. But must this always be the case? We use a combination of computational modeling with novel phase retrieval techniques and polarization-dependent vector wavefront shaping to explore the creation of computer-generated holographic beams. We discuss how to apply this method to creating obscured beams, such as uniformly enclosed optical bottle beams. and the properties these types of beams possess.

Constant magnetic fields are known to interact with electrically charged particles inducing Lorentz forces that point in a direction perpendicular to the field. However, if the particle is electrically discharged, it is impossible to induce a force using a constant magnetic field. An exotic option is to mimic a magnetic charge on a neutral particle. This false magnetic monopole will interact with the magnetic field just as an electric charge would do with an electric field through the Coulomb interaction. Attempts to generate this magnetic charge have mainly relied on quasiparticles generated using condensed matter spin ice networks. In this work we present another option based on neutral magneto-optical particles illuminated by a spinning monochromatic light field. We will analyze the behavior of these particles under different isotropic optical configurations, and we will calculate the value of the induced magnetic charge.

In this paper, we present an innovative optofluidic system that leverages cascaded bowtie photonic crystal (BPhC) to achieve subwavelength-scale control of temperature and fluid motion. The strong electromagnetic field enhancement of the bowtie structure can generate a hotspot at the resonance of BPhC, due to the absorption of bulk water in the infrared wavelength range (around 1600 nm). With the assistance of a cationic surfactant, cetyltrimethylammonium chloride (CTAC), a thermoelectric field is established to attract particles towards the hot region. Our experiments show that suspended particles as small as 800 nanometers can be rapidly transported to bowtie region and become trapped at the bowtie cavity on the resonance of BPhC. The trapped particles can be released simply by tuning the wavelength from on to off resonant conditions. Our work paves the way for non-plasmonic nanophotonics to manipulate microfluidic dynamics and precisely control trapping by tuning the wavelength

Optothermal and optofluidic manipulation have emerged as effective techniques for the precise control over particles, cells, and biomolecules through the interplay of optical, thermal, and hydrodynamic forces. In this study, we demonstrate that meticulous 3D engineering of thermal landscapes can induce both short- and long-range microfluidic flows to create optofluidic obstacles to guide, trap, and sort microparticles. By utilizing spatial light modulation to locally control temperature fields, we can generate a variety of microfluidic actuators, including pumps, traps, and valves. This flexibility in designing the optofluidic environment offers a comprehensive toolbox for a wide range of applications within microfluidics.

Mechanical forces play a pivotal role in cellular adhesions, where a vast array of proteins interacts with the cell cytoskeleton, affecting focal adhesions and adherens junctions, and regulating cell behavior and fate. To directly observe such events, we developed an experimental assay that combines several advanced single molecule techniques. Here, ultrafast force-clamp spectroscopy is employed to directly probe the force-dependence of molecular interactions between a single actin filament and a binding protein with sub-ms time resolution. Stabilization of the microscope through local gradient localization enables the resolution of protein conformational changes and binding position with sub-nm accuracy. An experimental arrangement, termed oriented dumbbell, allows us to determine the actin filament orientation and, thus, asymmetries in the force response of the interacting proteins. We applied our methodology to the interaction between α-catenin and F-actin, revealing that α-catenin switches between a slip and an asymmetric cooperative catch-bond with F-actin. This mechanism may underlie fluid-to-solid phase transitions that occur at the membrane-cytoskeleton interface.

Laser-based techniques offer powerful tools for studying the complex cellular mechanisms underlying neurodegeneration and neuroprotection. Laser scissors enable the precise induction of axonal injury, allowing investigation into axonal degenerative processes and evaluation of potential neuroprotective treatments. Laser scissors can also be utilized to kill a single cell and monitor the response in nearby astrocytes. For example, using this method, we found that a single-cell death can be disruptive to spontaneous calcium activity in surrounding cells. Additionally, focused lasers can be utilized to induce cavitation bubbles that produce shockwaves and subject cells to conditions like those experienced during a blast-induced traumatic brain injury. This allows us to have a window into the immediate cellular responses to traumatic brain injury and investigate potential mechanisms that may be targeted to mitigate damage. Laser-induced shockwaves have allowed us to study calcium signaling in response to nearby injury and determine that the immediate calcium response differs between cells that die and stay alive.

T cell clones can exhibit varying potencies towards their cognate peptide major histocompatibility complex molecule (pMHC), which may not be seen in traditional bulk assays. Performing single molecule and single cell experiments, including profiling through Single Cell Activation Requirements allow for further discrimination and selection of the highest quality clones. Using these techniques will help reveal how T cells function and advance screening methods for selecting the best T cells to use therapeutically.

We use a combination of optical trapping, microfluidics, and fluorescence microscopy to track individual, motile E. coli cells during infection by fluorescently labeled bacteriophages. Dual-trap optical tweezers immobilize swimming cells in a flow chamber, into which phages can be perfused. We measure the absorption of phages onto the cell surface with fluorescence imaging, while simultaneously monitoring the cell’s flagellar rotation with the optical traps. Utilizing the flagellar rotation frequency as a proxy for proton motive force, we examine phage-induced changes to E. coli’s membrane potential. These measurements reveal perturbations to host membrane integrity by phage attachment, followed by its recovery. This technique allows us to illuminate for the kinetics of viral infection of cells at the level of individual phages and bacteria.

In counter propagating plane waves, spherical beads occupy the interference fringes and optically bind with separations of around a wavelength. The binding strength depends on particle size and refractive index with the particle arrangement also dependent on the polarisation. Some combinations of refractive index and size do not optically bind: instead, the particles experience a force in the propagation direction that leads to a transition to longitudinal binding. These instabilities are assessed computationally with different particle numbers and polarisation states.

Active matter is based on the concepts of nonequilibrium thermodynamics applied to the most diverse disciplines. Active Brownian particles, unlike their passive counterparts, self-propel and give rise to complex behaviors distinctive of active matter. As the field is relatively recent, active matter still lacks curricular inclusion. Here, we propose macroscopic experiments using Hexbugs, a commercial toy robot, demonstrating effects peculiar of active systems, such as the setting into motion of passive objects via active particles, the sorting of active particles based on their mobility and chirality. Additionally, we provide a demonstration of Casimir-like attraction between planar objects mediated by active particles.

Optical nanotweezers are actively investigated as a powerful means to reversibly trap and study the properties of nanoscale biological objects and nanoparticles. To ensure that the objects can be reversibly trapped and released on demand, while also preventing undesired adsorption onto surfaces, surface passivation is of paramount importance. Although the surface chemistries examined in this study hold broad applicability across diverse nanotweezing platforms, our investigation primarily focuses on the newly reported Geometry-induced Electrohydrodynamic Tweezers (GET) as the nanotweezing platform. Geometry-induced electrohydrodynamic tweezer (GET) is a scalable and high-throughput technique for trapping and manipulating nanoscale objects. Here, we are investigating the antifouling properties of a GET nanotweezer passivated with Poly(ethylene glycol) methyl ether thiol (PEG), (1-Mercaptoundec-11-yl)tetra(ethylene glycol) (OEG), 11-Mercaptoundecanoic acid (MUA) and 1-Mercapto-11-hydroxy-3,6,9-trioxaundecane (DMOL). The confirmation of the passivated surfaces' wettability and the SAM vibrational properties is achieved through contact angle analysis and FTIR spectroscopy respectively.