The complexities of ligand/receptor interactions: Exploring the role of molecular vibrations and quantum tunnelling.

Molecular vibrations and quantum tunneling may link ligand binding to the function of pharmacological receptors. The well-established lock-and-key model explains a ligand's binding and recognition by a receptor; however, a general mechanism by which receptors translate binding into activation, inactivation, or modulation remains elusive. The Vibration Theory of Olfaction was proposed in the 1930s to explain this subset of receptor-mediated phenomena by correlating odorant molecular vibrations to smell, but a mechanism was lacking. In the 1990s, inelastic electron tunneling was proposed as a plausible mechanism for translating molecular vibration to odorant physiology. More recently, studies of ligands' vibrational spectra and the use of deuterated ligand analogs have provided helpful information to study this admittedly controversial hypothesis in metabotropic receptors other than olfactory receptors. In the present work, based in part on published experiments from our laboratory using planarians as an experimental organism, I will present a rationale and possible experimental approach for extending this idea to ligand-gated ion channels.

Impact of Single-Melamine Tautomerization on the Excitation of Molecular Vibrations in Inelastic Electron Tunneling Spectroscopy.

Vibrational quanta of melamine and its tautomer are analyzed at the single-molecule level on Cu(100) with inelastic electron tunneling spectroscopy. The on-surface tautomerization gives rise to markedly different low-energy vibrational spectra of the isomers, as evidenced by a shift in mode energies and a variation in inelastic cross sections. Spatially resolved spectroscopy reveals the maximum signal strength on an orbital nodal plane, excluding resonant inelastic tunneling as the mechanism underlying the quantum excitations. Decreasing the probe-molecule separation down to the formation of a chemical bond between the melamine amino group and the Cu apex atom of the tip leads to a quenched vibrational spectrum with different excitation energies. Density functional and electron transport calculations reproduce the experimental findings and show that the shift in the quantum energies applies to internal molecular bending modes. The simulations moreover suggest that the bond formation represents an efficient manner of tautomerizing the molecule.

GPCR Signaling: A Study of the Interplay Between Structure, Energy, and Function.

G protein-coupled receptors (GPCRs) exemplify sophisticated allosteric communication, transducing extracellular signals through ligand-induced structural rearrangements that resonate through the molecular scaffold. Despite extensive study, the biophysical underpinnings of how conformational changes spread remain unclear. This work employs a novel physics-based framework to characterize the role of energy dissipation in directing intramolecular signaling pathways. By modeling each residue as a network of coupled oscillators, we generate a localization landscape depicting the vibrational energy distribution throughout the protein scaffold. Quantifying directional energy flux between residues reveals distinct pathways for energy and information transfer, illuminating sequences of allosteric communication. Our analysis of CB1 and CCR5 crystal structures unveils an anisotropic pattern of energy dissipation aligning with key functional dynamics, such as activation-related conformational changes. These anisotropic patterns of vibrational energy flow constitute pre-configured channels for allosteric signaling. Elucidating the relationship between structural topology and energy dissipation patterns provides key insights into the thermodynamic drivers of conformational signaling. This methodology significantly advances our mechanistic understanding of allostery in GPCRs and presents a broadly applicable approach for rationally dissecting allosteric communication pathways, with potential implications for structure-based drug design targeting these critical receptors.

Fast vibrational analysis of molecular systems.

The development of infrared difference spectroscopy provides unprecedented insights on structures of complex molecules like metalloproteins. However, the relevant information can be hard to find among the many bands of the vibrational spectra. The ab initio modeling is very helpful to assign the frequencies to vibrational modes but it is a challenge to process the huge quantity of data into descriptors useful for experimentalists. To this end, we developed a new tool called VIBMOL allowing to analyze vibrational modes of molecules from hessian matrices calculated with common quantum chemistry codes. VIBMOL program runs on Unix machines. Through a new graphical interface, the users can calculate the normal modes of molecules, visualize them, simulate infrared spectra, and explore the Potential Energy Distribution of normal modes among any set of vibration coordinates. It is combined with an interface program (gosdmu) formatting relevant data from the GAUSSIAN program. VIBMOL code is available upon request to the authors. A discussion is provided to help the readers to choose between a large choice of different software and it shows how VIBMOL can make the IR assignment easier in the context of collaborations with experimentalists.

Interpretation of molecular electron transport in ab initio many-electron framework incorporating zero-point nuclear motion effects.

A computational methodology, founded on chemical concepts, is presented for interpreting the role of nuclear motion in the electron transport through single-molecule junctions (SMJ) using many-electron ab initio quantum chemical calculations. Within this approach the many-electron states of the system, computed at the SOS-ADC(2) level, are followed along the individual normal modes of the encapsulated molecules. The inspection of the changes in the partial charge distribution of the many-electron states allows the quantification of the electron transport and the estimation of transmission probabilities. This analysis improves the understanding of the relationship between internal motions and electron transport. Two SMJ model systems are studied for validation purposes, constructed from a conductor (BDA, benzene-1,4-diamine) and an insulator molecule (DABCO, 1,4-diazabicyclo[2.2.2]octane). The trends of the resulting transmission probabilities are in agreement with the experimental observations, demonstrating the capability of the approach to distinguish between conductor and insulator type systems, thereby offering a straightforward and cost-effective tool for such classifications via quantum chemical calculations.

Acoustic noise reduction in the NexGen 7 T scanner.

PURPOSE: Driven by the Lorentz force, acoustic noise may arguably be the next physiological challenge associated with ultra-high field MRI scanners and powerful gradient coils. This work consisted of isolating and mitigating the main sound pathway in the NexGen 7 T scanner equipped with the investigational Impulse head gradient coil. METHODS: Sound pressure level (SPL) measurements were performed with and without the RF coil to assess its acoustic impact. Vibration measurements were carried out on the gradient coil, the RF coil, and on the patient table to distinguish the different vibration mechanisms and pathways. Vibrations of the RF coil were modified by either making contact with the patient bore liner with padding material or by changing directly the RF shield with phosphor bronze mesh material. RESULTS: SPL and vibration measurements demonstrated that eddy-currents induced in the RF shield were the primary cause of acoustic noise. Replacing the conventional solid copper shield with phosphor bronze mesh material altered the vibrations of the RF shield and decreased SPL by 6 to 8 dB at the highest frequencies in EPI, depending on the gradient axis, while boosting the transmit B1 + field by 15%. Padding led to slightly less sound reduction on the X and Z gradient axes, but with minimal impact for the Y axis. CONCLUSION: This study demonstrates the potential importance of eddy-current induced vibrations in the RF coil in terms of acoustic noise and opens new horizons for mitigation measures.

Gradient-induced vibrations and motion-induced Lenz effects on conductive nonmagnetic orthopedic implants in MRI.

PURPOSE: To quantify the extent of gradient-induced vibrations, and the magnitude of motion-induced displacement forces ("Lenz effect"), in conductive nonmagnetic orthopedic prostheses. METHODS: The investigation is carried out through numerical simulations, for a 3 T scanner. For gradient-induced torques and vibrations, a knee and a shoulder implant are considered, at dB/dt equal to 42 T/s (rms). For motion-induced forces associated with the Lenz effect, a knee and a hip implant are studied, considering a patient who translates on the examination couch, or walks next to it. RESULTS: Gradient-induced torques may be within the same order of magnitude as the worst case gravitational torque defined in the ASTM standards. However, for all investigated cases, they result to be lower. In vacuum, the extent of the corresponding vibration reduces with frequency. At the lowest investigated frequency (270 Hz), it keeps below 25 µm. For an implant partially embedded in bone, the extent of the vibration increases with frequency. Nevertheless, the displacement is far lower than the worst case observed in vacuum (negligible in contact with the bone; ˜1 µm or less where the implant emerges from the bone). The Lenz effect induced by the motion of the patient through the stationary magnetic field produces forces on the order of a few millinewtons (i.e., at least two orders of magnitude lower than the implant weight). CONCLUSION: Comparing the results with mechanical loads caused by ordinary activities of daily living, and with the levels of tolerable micromotions, a good safety margin is confirmed.

Modeling Anharmonic Effects in the Vibrational Spectra of High-Frequency Modes.

High-resolution vibrational spectra of C-H, O-H, and N-H stretches depend on both molecular conformation and environment as well as provide a window into the frequencies of many other vibrational degrees of freedom as a result of mode mixing. We review current theoretical strategies that are being deployed to both aid and guide the analysis of the data that are encoded in these spectra. The goal is to enhance the power of vibrational spectroscopy as a tool for probing conformational preferences, hydrogen bonding effects away from equilibrium, and energy flow pathways. Recent years have seen an explosion of new methods and strategies for solving the nuclear Schrödinger equation. Rather than attempt a comprehensive review, this work highlights specific molecular systems that we have chosen as representing bonding motifs that are important to chemistry and biology. We focus on the choices theoretical chemists make regarding the level of electronic structure theory, the representation of the potential energy surface, the selection of coordinates, preferences in basis sets, and methods of solution.

On the function of a female-like signal type in the vibrational repertoire of Enchenopa male treehoppers (Hemiptera: Membracidae).

Animals often mimic the behaviours or signals of conspecifics of the opposite sex while courting. We explored the potential functions of a novel female-like signal type in the courtship displays of male Enchenopa treehoppers. In these plant-feeding insects, males produce plant-borne vibrational advertisement signals, to which females respond with their own duetting signals. Males also produce a signal type that resembles the female duetting responses. We experimentally tested whether this signal modifies the behaviour of receivers. First, we tested whether the female-like signal would increase the likelihood of a female response. However, females were as likely to respond to playbacks with or without them. Second, we tested whether the female-like signal would inhibit competing males, but males were as likely to produce displays after playbacks with or without them. Hence, we found no evidence that this signal has an adaptive function, despite its presence in the courtship display, where sexual selection affects signal features. Given these findings, we also explored whether the behavioural and morphological factors of the males were associated with the production of the female-like signal. Males that produced this signal had higher signalling effort (longer and more frequent signals) than males that did not produce it, despite being in worse body condition. Lastly, most males were consistent over time in producing the female-like signal or not. These findings suggest that condition-dependent or motivational factors explain the presence of the female-like signal. Alternatively, this signal might not bear an adaptive function, and it could be a way for males to warm up or practice signalling, or even be a by-product of how signals are transmitted through the plant. We suggest further work that might explain our puzzling finding that a signal in the reproductive context might not have an adaptive function.

Antlion larvae localize long distant preys by a mechanism based on time difference.

Pit building antlions Euroleon nostras have been submitted to artificial cues in order to delineate their faculty to localize a prey. Series of propagating pulses in sand have been created from an extended source made of 10 piezoelectric transducers equally spaced on a line and located at a large distance from the pit. The envelope of each pulse encompasses six oscillations at a carrier frequency of 1250 Hz and up to eight oscillations at 1666 Hz. In one set of experiments, the first wave front is followed by similar wave fronts and the antlions respond to the cue by throwing sand in the opposite direction of the wave front propagation direction. In another set of experiments, the first wave front is randomly spatially structured while the propagation of the wave fronts inside the envelope of the pulse are not. In that case, the antlions respond less to the cue by throwing sand, and when they do, their sand throwing is more randomly distributed in direction. The finding shows that the localization of vibration signal by antlions are based on the equivalent for hearing animals of interaural time difference in which the onset has more significance than the interaural phase difference.

Biomechanical properties of non-flight vibrations produced by bees.

Bees use thoracic vibrations produced by their indirect flight muscles for powering wingbeats in flight, but also during mating, pollination, defence and nest building. Previous work on non-flight vibrations has mostly focused on acoustic (airborne vibrations) and spectral properties (frequency domain). However, mechanical properties such as the vibration's acceleration amplitude are important in some behaviours, e.g. during buzz pollination, where higher amplitude vibrations remove more pollen from flowers. Bee vibrations have been studied in only a handful of species and we know very little about how they vary among species. In this study, we conducted the largest survey to date of the biomechanical properties of non-flight bee buzzes. We focused on defence buzzes as they can be induced experimentally and provide a common currency to compare among taxa. We analysed 15,000 buzzes produced by 306 individuals in 65 species and six families from Mexico, Scotland and Australia. We found a strong association between body size and the acceleration amplitude of bee buzzes. Comparison of genera that buzz-pollinate and those that do not suggests that buzz-pollinating bees produce vibrations with higher acceleration amplitude. We found no relationship between bee size and the fundamental frequency of defence buzzes. Although our results suggest that body size is a major determinant of the amplitude of non-flight vibrations, we also observed considerable variation in vibration properties among bees of equivalent size and even within individuals. Both morphology and behaviour thus affect the biomechanical properties of non-flight buzzes.

Setting up a light microscopy core facility: Facility design.

The successful operation of a light microscopy core facility depends also on the initial setup of its infrastructure. This article covers the aspects of location selection and room planning and what environmental factors need to be considered. These include light, temperature, vibrations as well as the basic installations needed for microscope operation.

Investigating and exploiting the impact of variability in resonator parameters on the vibration attenuation in locally resonant metamaterials.

Locally resonant metamaterials (LRMs) have recently emerged in the search for lightweight noise and vibration solutions. These materials have the ability to create stop bands, which arise from the sub-wavelength addition of identical resonators to a host structure and result in strong vibration attenuation. However, their manufacturing inevitably introduces variability such that the system as-manufactured often deviates significantly from the original as-designed. This can reduce attenuation performance, but may also broaden the attenuation band. This work focuses on the impact of variability within tolerance ranges in resonator properties on the vibration attenuation in metamaterial beams. Following a qualitative pre-study, two non-intrusive uncertainty propagation approaches are applied to find the upper and lower bounds of three performance metrics, by evaluating deterministic metamaterial models with uncertain parameters defined as interval variables. A global search approach is used and compared with a machine learning (ML)-based uncertainty propagation approach which significantly reduces the required number of simulations. Variability in resonator stiffnesses and masses is found to have the highest impact. Variability in the resonator positions only has a comparable impact for less deep sub-wavelength designs. The broadening potential of varying resonator properties is exploited in broadband optimization and the robustness of the optimized metamaterial is assessed.This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 2)'.

The possible influence of third-order shim coils on gradient-magnet interactions: an inter-field and inter-site study.

OBJECTIVE: To assess the possible influence of third-order shim coils on the behavior of the gradient field and in gradient-magnet interactions at 7 T and above. MATERIALS AND METHODS: Gradient impulse response function measurements were performed at 5 sites spanning field strengths from 7 to 11.7 T, all of them sharing the same exact whole-body gradient coil design. Mechanical fixation and boundary conditions of the gradient coil were altered in several ways at one site to study the impact of mechanical coupling with the magnet on the field perturbations. Vibrations, power deposition in the He bath, and field dynamics were characterized at 11.7 T with the third-order shim coils connected and disconnected inside the Faraday cage. RESULTS: For the same whole-body gradient coil design, all measurements differed greatly based on the third-order shim coil configuration (connected or not). Vibrations and gradient transfer function peaks could be affected by a factor of 2 or more, depending on the resonances. Disconnecting the third-order shim coils at 11.7 T also suppressed almost completely power deposition peaks at some frequencies. DISCUSSION: Third-order shim coil configurations can have major impact in gradient-magnet interactions with consequences on potential hardware damage, magnet heating, and image quality going beyond EPI acquisitions.

Soft-Tissue Vibrations and Fatigue During Prolonged Running: Does an Individualized Midsole Hardness Play a Role?

Footwear has the potential to reduce soft-tissue vibrations (STV) but responses are highly subject-specific. Recent evidence shows that compressive garments minimizing STV have a beneficial effect on neuromuscular (NM) fatigue. The aim was to determine whether an individualized midsole hardness can minimize STV and NM fatigue during a half marathon. Twenty experienced runners were recruited for three visits: a familiarization session including the identification of midsole minimizing and maximizing STV amplitude (MIN and MAX, respectively), and two half marathon sessions at 95% of speed at the second ventilatory threshold. STV of the gastrocnemius medialis (GM) muscle, running kinetics, foot strike pattern, rating perceived exhaustion (RPE), and midsole liking were recorded every 3 km. NM fatigue was assessed on plantar flexors (PF) before (PRE) and after (POST) the half marathon. At POST, PF central and peripheral alterations and changes in contact time, step frequency, STV median frequency, and impact force frequency as well as foot strike pattern were found in both MIN and MAX. No significant differences in damping, STV main frequency, flight time, duty factor, and loading rate were observed between conditions whatever the time period. During the half marathon, STV amplitude of GM significantly increased over time for the MAX condition (+13.3%) only. Differences between MIN and MAX were identified for RPE and midsole liking. It could be hypothesized that, while significant, the effect of midsole hardness on STV is too low to substantially affect NM fatigue.

Liquid walls and interfaces in arbitrary directions stabilized by vibrations.

Gravity shapes liquids and plays a crucial role in their internal balance. Creating new equilibrium configurations irrespective of the presence of a gravitational field is challenging with applications on Earth as well as in zero-gravity environments. Vibrations are known to alter the shape of liquid interfaces and also to change internal dynamics and stability in depth. Here, we show that vibrations can also create an "artificial gravity" in any direction. We demonstrate that a liquid can maintain an inclined interface when shaken in an arbitrary direction. A necessary condition for the equilibrium to occur is the existence of a velocity gradient determined by dynamical boundary conditions. However, the no-slip boundary condition and incompressibility can perturb the required velocity profile, leading to a destabilization of the equilibrium. We show that liquid layers provide a solution, and liquid walls of several centimeters in height can thus be stabilized. We show that the buoyancy equilibrium is not affected by the forcing.

Improving light availability and creating high-frequency light-dark cycles in raceway ponds through vortex-induced vibrations for microalgae cultivation: a fluid dynamic study.

Limited light availability due to insufficient vertical mixing strongly reduces the applicability of raceway ponds (RWPs). To overcome this and create light-dark (L/D) cycles for enhanced biomass production through improved vertical mixing, vortex-induced vibration (VIV) system was implemented by the authors in a previous study to an existing pilot-scale RWP. In this study, experimental characterization of fluid dynamics for VIV-implemented RWP is carried out. Particle image velocimetry (PIV) technique is applied to visualize the flow. The extents of the vertical mixing due to VIV and the characteristics of L/D cycles were examined by tracking selected particles. Pond depth was hypothetically divided into three zones, namely dark, light Iimited and light saturated for detailed analysis of cell trajectories. It has been observed that VIV cylinder oscillation can efficiently facilitate the transfer of cells from light-limited to light-saturated zones. Among the cells that were tracked, 44% initially at dark zone entered the light-limited zone and 100% of initially at light-limited zone entered the light-saturated zone. 33% of all tracked cells experienced high-frequency L/D cycles with an average frequency of 35.69 s-1 and 0.49 light fraction. The impact of VIV was not discernible in the deeper sections of the pond, due to constrained oscillation amplitudes. Our findings suggest that the approximately 20% increase in biomass production reported in our previous study can be attributed to the synergistic effects of enhanced L/D cycle frequencies and improved light availability resulting from the transfer of cells from dark to light-limited zones. To further enhance the effectiveness of VIV, design improvements were developed. It was concluded that light availability could be significantly improved with the presented method for more effective use of RWPs.

Passive Control in a Continuous Beam under a Traveling Heavy Mass: Dynamic Response and Experimental Verification.

The motion of a heavy mass on a bridge span causes vibrations whose magnitude and frequency content depend on the mechanical properties of the structural system, including the magnitude of that mass and its speed of traverse. In order to limit vibrations that could potentially cause damage, a simple passive device configuration, namely the tuned mass damper (TMD), is introduced and its effect on the beam vibrations analyzed. Specifically, a TMD in the form of a single-degree-of-freedom (SDOF) unit comprising a mass and a spring is placed on the span to act as a secondary system for absorbing vibrations from the primary system, i.e., the bridge itself. A Lagrangian energy balance formulation is used to derive the governing equations of motion, followed by an analytical solution using the Laplace transform to investigate the transmission of vibratory energy between primary and secondary systems. Results are given in terms of time histories, Fourier spectra and spectrograms, where the influence of the TMD in reducing vibratory energy is demonstrated. The TMD is placed in the region where the beam's transverse motion is at a maximum, while its mechanical properties are sub-optimal, in the sense that there is no separate damper present and minimal damping is provided by the spring element itself. In parallel with the analysis, a series of experiments involving a simply supported model steel bridge span traversed by a heavy mass are conducted to first gauge the analytical solution and then to confirm the validity of the proposed passive scheme.

Experimental Evaluation of Pedestrian-Induced Multiaxial Gait Loads on Footbridges: Effects of the Structure-to-Human Interaction by Lateral Vibrating Platforms.

The introduction of resistant and lightweight materials in the construction industry has led to civil structures being vulnerable to excessive vibrations, particularly in footbridges exposed to human-induced gait loads. This interaction, known as Human-Structure Interaction (HSI), involves a complex interplay between structural vibrations and gait loads. Despite extensive research on HSI, the simultaneous effects of lateral structural vibrations with fundamental frequencies close to human gait frequency (around 1.0 Hz) and wide amplitudes (over 30.0 mm) remain inadequately understood, posing a contemporary structural challenge highlighted by incidents in iconic bridges like the Millennium Bridge in London, Solferino Bridge in Paris, and Premier Bridge in Cali, Colombia. This paper focuses on the experimental exploration of Structure-to-Human Interaction (S2HI) effects using the Human-Structure Interaction Multi-Axial Test Framework (HSI-MTF). The framework enables the simultaneous measurement of vertical and lateral loads induced by human gait on surfaces with diverse frequency ranges and wide-amplitude lateral harmonic motions. The study involved seven test subjects, evaluating gait loads on rigid and harmonic lateral surfaces with displacements ranging from 5.0 to 50.0 mm and frequency content from 0.70 to 1.30 Hz. A low-cost vision-based motion capture system with smartphones analyzed the support (Tsu) and swing (Tsw) periods of human gait. Results indicated substantial differences in Tsu and Tsw on lateral harmonic protocols, reaching up to 96.53% and 58.15%, respectively, compared to rigid surfaces. Normalized lateral loads (LL) relative to the subject's weight (W0) exhibited a linear growth proportional to lateral excitation frequency, with increased proportionality constants linked to higher vibration amplitudes. Linear regressions yielded an average R2 of 0.815. Regarding normalized vertical load (LV) with respect to W0, a consistent behavior was observed for amplitudes up to 30.0 mm, beyond which a linear increase, directly proportional to frequency, resulted in a 28.3% increment compared to rigid surfaces. Correlation analyses using Pearson linear coefficients determined relationships between structural surface vibration and pedestrian lateral motion, providing valuable insights into Structure-to-Human Interaction dynamics.

Novel Framework for Quality Control in Vibration Monitoring of CNC Machining.

Vibrations are a common issue in the machining and metal-cutting sector, in which the spindle vibration is primarily responsible for the poor surface quality of workpieces. The consequences range from the need to manually finish the metal surfaces, resulting in time-consuming and costly operations, to high scrap rates, with the corresponding waste of time and resources. The main problem of conventional solutions is that they address the suppression of machine vibrations separately from the quality control process. In this novel proposed framework, we combine advanced vibration-monitoring methods with the AI-driven prediction of the quality indicators to address this problem, increasing the quality, productivity, and efficiency of the process. The evaluation shows that the number of rejected parts, time devoted to reworking and manual finishing, and costs are reduced considerably. The framework adopts a generalized methodology to tackle the condition monitoring and quality control processes. This allows for a broader adaptation of the solutions in different CNC machines with unique setups and configurations, a challenge that other data-driven approaches in the literature have found difficult to overcome.