Mechanical Crosstalk Research Articles

Impact of ionizing radiation on cell-ECM mechanical crosstalk in breast cancer.

The stiffness of the extracellular matrix plays a crucial role in cell motility and spreading, influencing cell morphology through cytoskeleton organization and transmembrane proteins' expression. In this context, mechanical characterization of both cells and the extracellular matrix gains prominence for enhanced diagnostics and clinical decision-making. Here, we investigate the combined effect of mechanotransduction and ionizing radiations on altering cells' mechanical properties, analysing mammary cell lines (MCF10A and MDA-MB-231) after X-ray radiotherapy (2 and 10Gy). We found that ionizing radiations sensitively affect adenocarcinoma cells cultured on substrates mimicking cancerous tissue stiffness (15kPa), inducing an increased structuration of paxillin-rich focal adhesions and cytoskeleton: this process translates in the augmentation of tension at the actin filaments level, causing cellular stiffness and consequently affecting cytoplasmatic/nuclear morphologies. Deeper exploration of the intricate interplay between mechanical factors and radiation should provide novel strategies to orient clinical outcomes.

Mitigation of mechanical cross-talk in resonant beam accelerometers

Mitigation of mechanical cross-talk in resonant beam accelerometers

Mechanical crosstalk between the intervertebral disc, facet joints, and vertebral endplate following acute disc injury in a rabbit model.

Vertebral endplate sclerosis and facet osteoarthritis have been documented in animals and humans. However, it is unclear how these adjacent pathologies engage in crosstalk with the intervertebral disc. This study sought to elucidate this crosstalk by assessing each compartment individually in response to acute disc injury. Eleven New Zealand White rabbits underwent annular disc puncture using a 16G or 21G needle. At 4 and 10 weeks, individual compartments of the motion segment were analyzed. Discs underwent T 1 relaxation mapping with MRI contrast agent gadodiamide as well T 2 mapping. Both discs and facets underwent mechanical testing via vertebra-disc-vertebra tension-compression creep testing and indentation testing, respectively. Endplate bone density was quantified via μCT. Discs and facets were sectioned and stained for histology scoring. Intervertebral discs became more degenerative with increasing needle diameter and time post-puncture. Bone density also increased in endplates adjacent to both 21G and 16G punctured discs leading to reduced gadodiamide transport at 10 weeks. The facet joints, however, did not follow this same trend. Facets adjacent to 16G punctured discs were less degenerative than facets adjacent to 21G punctured discs at 10 weeks. 16G facets were more degenerative at 4 weeks than at 10, suggesting the cartilage had recovered. The formation of severe disc osteophytes in 16G punctured discs between 4 and 10 weeks likely offloaded the facet cartilage, leading to the recovery observed. Overall, this study supports that degeneration spans the whole spinal motion segment following disc injury. Vertebral endplate thickening occurred in response to disc injury, which limited the diffusion of small molecules into the disc. This work also suggests that altered disc mechanics can induce facet degeneration, and that extreme bony remodeling adjacent to the disc may promote facet cartilage recovery through offloading of the articular cartilage.

The mechanisms crosstalk and therapeutic opportunities between ferroptosis and ovary diseases.

Ferroptosis, a form of regulated cell death, was first defined in 2012. Ferroptosis mainly involves iron-driven lipid peroxidation damage of cells. This process is regulated by iron homeostasis, redox balance, lipid metabolism, glutathione metabolism, and various disease signaling pathways. Iron is one of the key mineral elements that regulate the physiological function of women and the development of ovarian tumors. Occurrence of Ferroptosis has some hidden dangers and advantages in ovary diseases. Some scholars have shown that ferroptosis of ovarian granulosa cells (GC) promotes the development of ovarian dysfunction and polycystic ovary syndrome (PCOS). Interestingly, drug-resistant ovarian cancer cells are very sensitive to ferroptosis, suggesting that pharmacological positive and negative regulation of ferroptosis has great potential in the treatment of benign ovarian diseases and ovarian cancer. This article aimed to assess how ferroptosis occurs and the factors controlling ferroptosis. Moreover, we summarize how ferroptosis can be used to predict, diagnose and target treatment ovary disease. Meanwhile, we also evaluated the different phenomena of Ferroptosis in ovarian diseases. It aims to provide new directions for the research and prevention of female reproductive diseases.

Crosstalk-free large aperture electromagnetic 2D micromirror for LiDAR application

This paper presents a novel design of a 2D electromagnetic micromirror without crosstalk. The proposed micromirror uses a flexible printed circuit board (FPCB) and four layers of coils embedded in the polyimide layers. The insulated layers of the coil allow for independent actuation of the mirror plate to rotate about two orthogonal axes. The diamond shaped micromirror uses a hyperbola-shaped magnetic field on the coils under the mirror plate and a 45-degrees magnetic field on the coils embedded in the FPCB frame to eliminate the mechanical crosstalk. Finite element analysis was used to predict the novel 2D micromirror’s behavior. The novel 2D micromirror prototype is used in scanning LiDAR, The results indicate that the crosstalk-free pattern yielded significantly clearer results, particularly for detecting object boundaries and reducing barrel distortion. The experimental test has verified the novel crosstalk-free 2D micromirror working principle and showed good scanning quality: no crosstalk and an improvement in the horizontal field of view up to 19% But with the cost of reducing the vertical field of view by up to 12%. The novel 2D micromirror prototype has a large aperture of 19 × 19 mm2, which is very suitable for coaxial scanning LiDAR.

Endothelium and Subendothelial Matrix Mechanics Modulate Cancer Cell Transendothelial Migration.

Cancer cell extravasation, a key step in the metastatic cascade, involves cancer cell arrest on the endothelium, transendothelial migration (TEM), followed by the invasion into the subendothelial extracellular matrix (ECM) of distant tissues. While cancer research has mostly focused on the biomechanical interactions between tumor cells (TCs) and ECM, particularly at the primary tumor site, very little is known about the mechanical properties of endothelial cells and the subendothelial ECM and how they contribute to the extravasation process. Here, an integrated experimental and theoretical framework is developed to investigate the mechanical crosstalk between TCs, endothelium and subendothelial ECM during in vitro cancer cell extravasation. It is found that cancer cell actin-rich protrusions generate complex push-pull forces to initiate and drive TEM, while transmigration success also relies on the forces generated by the endothelium. Consequently,mechanical properties of the subendothelial ECM and endothelial actomyosin contractility that mediate the endothelial forces also impact the endothelium's resistance to cancer cell transmigration. These results indicate that mechanical features of distant tissues, including force interactions between the endothelium and the subendothelial ECM, are key determinants of metastatic organotropism.

Cell response to substrate energy dissipation outweighs rigidity sensing.

The mechanical properties of the extracellular matrix (ECM) are essential for tissue homeostasis, as they determine cell spreading, differentiation, proliferation and migration through the concerted action of mechanoresponsive proteins such as YAP. However, interpretation of the mechanical crosstalk between cells and the ECM using hydrogel mimetics has been limited by the intricacies to engineer viscoelasticity typical of the ECM, the difficulty in discerning viscoelastic from viscoplastic behaviors, and the convolution of their mechanical and non-mechanical properties. As a result, whether cells sense ECM energy dissipation (i.e. viscoelasticity) independently of stiffness remains unknown. Here, we exploit fundamental polypeptide conformational changes under force to produce titin-based protein hydrogels with tailored viscoelasticity and preserved chemical composition, ultrastructure, crosslinking density, and biochemical environment. Using our system, we demonstrate that cells respond to changes in viscoelastic cues only, as nuclear YAP decreases with substrate energy dissipation. Furthermore, the rate of YAP translocation to the nucleus is more sensitive to changes in energy dissipation than in stiffness; indicating that the response to the viscous component engineered into our ECM mimetics supersedes rigidity effects. This observation implies that cells perceive ECM rigidity and energy dissipation by non-overlapping mechanisms, illustrating the relevance of ECM viscoelasticity in the biology of the cell.

Activated EGFR-αVβ3 interactions directly drive integrin-mediated cell mechanics.

Cells sense and respond to physical forces, and aberrations in this exchange are implicated in disease and dysfunction. Integrins and EGFR have robust synergy, with integrins establishing the mechanical link between cytoskeleton and microenvironment and EGFR regulating growth and survival. Previously, we established ligand-activated EGFR tunes integrin mechanics and facilitates cell spreading and focal adhesion (FA) maturation. Sialylation enhanced this mechanical crosstalk by increasing retention of activated EGFR on the plasma membrane. However, the underlying mechanisms orchestrating EGFR's influence on cell mechanics remain unknown. To address if there was a direct interaction between EGFR and integrin, we used a proximity ligation assay. In Cos-7 cells, EGF stimulation increased EGFR-αVβ3 interactions at 1 hour post-plating over untreated controls. The number of interactions were reduced at 24 hours, indicating that they are transient and support initial cell attachment and FA formation. Sites of EGFR-αVβ3 interactions colocalize with paxillin and pFAK with higher efficiency at 1 hour than 24 hours, supporting their role in FA formation but not maintenance. EGFR-αVβ3integrin interactions were confirmed by co-immunoprecipitation with immunoblotting analysis. Applying high-resolution TIRF microscopy, we associate these interactions to lipid raft microdomains which indicate formation of EGFR-integrin based signaling hubs at the membrane to support downstream mechanical outcomes like FA formation. Finally, employing time-lapse live cell TIRF imaging of Cos-7 cells overexpressing tagged EGFR and paxillin we characterize the dynamic nature of EGFR-αVβ3 interactions and associate them with FAs. Activated EGFR accumulates at sites for FA formation before paxillin starts clustering and persists during FA maturation. Our results implicate direct EGFR-integrin interaction as the mechanism driving cellular outcomes including FA formation, maturation and cell spreading during initial cell adhesion. Overall, EGFR-integrin interplay performs a vital synergistic function as a joint-signaling rheostat orchestrating cell mechanics.

Shaped input for reducing crosstalk of two-axis MEMS scanners

We have proposed a pre-shaped input method to minimize the crosstalk of two-axis microelectromechanical system (MEMS) scanners. The mechanical and geometrical crosstalk of a two-axis MEMS scanner was estimated to mitigate the total crosstalk of the scan pattern in an image plane. The desired scan pattern was converted into a required mechanical scan angle to compensate for the geometrical crosstalk. The device used in this study was a two-axis gimbal-less MEMS scanner, whose experimental transfer functions were obtained in terms of the mechanical scan angle. The method was evaluated for one-axis driving, reducing the total crosstalk by an average of 23.1 and 2.78 times along the x- and y -axis, respectively. The method was extended to two-axis driving, reducing the total crosstalk by an average of 18.1 and 2.49 times along the x- and y -axis, respectively. The lower reduction in the y -axis can be explained by the fact that the geometrical crosstalk appears much more on the y -axis than x -axis in the present measurement setup. In conclusion, the high suppression of crosstalk experimentally indicates that this method can effectively mitigate the total crosstalk and will be helpful to improve the performance of MEMS scanners. • Pre-shaped input was applied to obtain desirable output for two-axis MEMS scanners. • Two-axis pre-shaped input was carried out to reduce the crosstalk in MEMS scanner. • Scan pattern was improved by removing optical and mechanical crosstalk.

Design and Characterization of Three-Axis High-Range Inductive Tactile Force Sensor Utilizing Magnetorheological Elastomer for Robotic Surgical Applications

This article presents a three-axis inductive tactile force sensor utilizing a magnetorheological elastomer (MRE) marker for inducing inductance change in square-shaped coils, in response to an input force. The sensor consists of copper coils on a printed circuit board (PCB) and a patterned elastomer layer between the marker and coils. The proposed configuration of the coils reduces the mechanical crosstalk between the applied three-axis forces, thus decoupling the force axes. Finite-element method (FEM)-based analyses are carried out to optimize the sensing gap between the coils and the marker. To observe the effect of the elastomer material on the sensor performance, two types of silicone rubbers, Ecoflex-30 and RTV-528, are used to make the patterned elastomer and the marker. The sensor with Ecoflex-30 elastomer can measure forces up to 25 N in normal and 2.5 N in shear directions, whereas the sensor with RTV-528 elastomer has a higher force range of up to 30 N for normal and 6 N for shear directions but has a lower sensitivity. A resolution of 12.71, 7.96, and 6.61 mN is achieved with Ecoflex-30, whereas for RTV-528, the force resolution is 76.52, 11.7, and 23.98 mN for normal, shear, and angular shear directions, respectively. The hysteresis error for the proposed sensors is 7.2% and 5.3% for Ecoflex-30 and RTV-528 elastomers, respectively. The proposed inductive tactile force sensor can be used in a wide range of robotic surgical applications for sensing multidirectional forces with better resolution and low hysteresis error.

The use of acoustic holography for simultaneous characterization of various focus steering configurations in ultrasound fields generated by multi-element phased arrays

Acoustic holography has been successfully applied for accurate characterization of ultrasound sources. However, its direct use for multi-element phased arrays with many possible field configurations is not feasible. Here, two methods based on transient acoustic holography are proposed allowing reconstruction of all field configurations over a range of frequencies. The methods were tested using a 2 MHz piezocomposite 12-element annular array. First, the holography measurement was performed with all array elements excited in phase. After field reconstruction on the array surface, each element was separated spatially. Second, the array elements were excited individually in sequence for each measurement location. After separating the measured signals in time, 12 separate holograms were obtained to representing each array element individually. For both methods, the array performance was predicted by numerically defining the phase of each element. To evaluate these predictions, a hologram for a specific case of focus steering toward the array was measured independently. Although both characterization methods captured the array performance with focus steering, the approach that extracts elements from time sequences provided higher accuracy and thus can be used for sources with stronger electrical and mechanical crosstalk between the elements. [Work supported by RSF-20-12-00145 and NIH R01EB025187.]

Epithelial cell cluster size affects force distribution in response to EGF-induced collective contractility

Several factors present in the extracellular environment regulate epithelial cell adhesion and dynamics. Among them, growth factors such as EGF, upon binding to their receptors at the cell surface, get internalized and directly activate the acto-myosin machinery. In this study we present the effects of EGF on the contractility of epithelial cancer cell colonies in confined geometry of different sizes. We show that the extent to which EGF triggers contractility scales with the cluster size and thus the number of cells. Moreover, the collective contractility results in a radial distribution of traction forces, which are dependent on integrin β1 peripheral adhesions and transmitted to neighboring cells through adherens junctions. Taken together, EGF-induced contractility acts on the mechanical crosstalk and linkage between the cell-cell and cell-matrix compartments, regulating collective responses.

Self-generated gradients steer collective migration on viscoelastic collagen networks.

Growing evidence suggests that the physical properties of the cellular microenvironment influence cell migration. However, it is not currently understood how active physical remodelling by cells affects migration dynamics. Here we report that cell clusters seeded on deformable collagen-I networks display persistent collective migration despite not showing any apparent intrinsic polarity. Clusters generate transient gradients in collagen density and alignment due to viscoelastic relaxation of the collagen networks. Combining theory and experiments, we show that crosslinking collagen networks or reducing cell cluster size results in reduced network deformation, shorter viscoelastic relaxation time and smaller gradients, leading to lower migration persistence. Traction force and Brillouin microscopy reveal asymmetries in force distributions and collagen stiffness during migration, providing evidence of mechanical cross-talk between cells and their substrate during migration. This physical model provides a mechanism for self-generated directional migration on viscoelastic substrates in the absence of internal biochemical polarity cues.

A Soft Multi-Axis High Force Range Magnetic Tactile Sensor for Force Feedback in Robotic Surgical Systems.

This paper presents a multi-axis low-cost soft magnetic tactile sensor with a high force range for force feedback in robotic surgical systems. The proposed sensor is designed to fully decouple the output response for normal, shear and angular forces. The proposed sensor is fabricated using rapid prototyping techniques and utilizes Neodymium magnets embedded in an elastomer over Hall sensors such that their displacement produces a voltage change that can be used to calculate the applied force. The initial spacing between the magnets and the Hall sensors is optimized to achieve a large displacement range using finite element method (FEM) simulations. The experimental characterization of the proposed sensor is performed for applied force in normal, shear and 45° angular direction. The force sensitivity of the proposed sensor in normal, shear and angular directions is 16 mV/N, 30 mV/N and 81 mV/N, respectively, with minimum mechanical crosstalk. The force range for the normal, shear and angular direction is obtained as 0–20 N, 0–3.5 N and 0–1.5 N, respectively. The proposed sensor shows a perfectly linear behavior and a low hysteresis error of 8.3%, making it suitable for tactile sensing and biomedical applications. The effect of the material properties of the elastomer on force ranges and sensitivity values of the proposed sensor is also discussed.

Sarcopenia and bone health: new acquisitions for a firm liaison.

Osteosarcopenia (OS) is a newly defined condition represented by the simultaneous presence of osteopenia/osteoporosis and sarcopenia, the main age-related diseases. The simultaneous coexistence of the two phenotypes derives from the close connection of the main target tissues involved in their pathogenesis: bone and muscle. These two actors constitute the bone-muscle unit, which communicates through a biochemical and mechanical crosstalk which involves multiple factors. Altered pattern of molecular pathways leads to an impairment of both the functionality of the tissue itself and the communication with the complementary tissue, composing the OS pathogenesis. Recent advances in the genetics field have provided the opportunity to delve deeper into the complex biological and molecular mechanisms underlying OS. Unfortunately, there are still many gaps in our understanding of these pathways, but it has proven essential to apply strategies such as exercise and nutritional intervention to counteract OS. New therapeutic strategies that simultaneously target bone and muscle tissue are limited, but recently new targets for the development of dual-action drug therapies have been identified. This narrative review aims to provide an overview of the latest scientific evidence associated with OS, a complex disorder that will pave the way for future research aimed at understanding the bone-muscle-associated pathogenetic mechanisms.

An Initial Exploration of Coupled Transient Mechanical and Electrochemical Behaviors in Lithium Ion Batteries

While lithium-ion batteries are the dominant technology in the energy storage market, aspects of these batteries remain a mystery. For example, better understanding of chemical and mechanical crosstalk, and transients thereof, may lead to increased cycle life and rate capability. Here, an ultrasound acoustic characterization technique is introduced to probe the electrode/electrolyte interface in operando using signal amplitude analysis. This technique gives insight into lithium-ion concentration accumulation and depletion at the electrode/electrolyte interface, and these findings are consistent with Dualfoil model simulations.

Design and calibration of an optically segmented single volume scatter camera for neutron imaging

The Optically Segmented Single Volume Scatter Camera (OS-SVSC) aims to image neutron sources for non-proliferation applications using the kinematic reconstruction of elastic double-scatter events. Our prototype system consists of 64 EJ-204 organic plastic scintillator bars, each measuring 5mm × 5mm × 200mm and individually wrapped in Teflon tape. The scintillator array is optically coupled to two silicon photomultiplier ArrayJ-60035 64P-PCB arrays, each comprised of 64 individual 6x6mm J-Series sensors arranged in an 8 × 8 array.We report on the design details, including component selections, mechanical design and assembly, and the electronics system. The described design leveraged existing off-the-shelf solutions to support the rapid development of a phase 1 prototype. Several valuable lessons were learned from component and system testing, including those related to the detector's mechanical structure and electrical crosstalk that we conclude originates in the commercial photodetector arrays and the associated custom breakout cards.We detail our calibration efforts, beginning with calibrations for the electronics, based on the IRS3D application-specific integrated circuits, and their associated timing resolutions, ranging from 3090ps. With electronics calibrations applied, energy and position calibrations were performed for a set of edge bars using 22Na and 90Sr, respectively, reporting an average resolution of 12.07±0.03mm for energy depositions between 900keVee and 1000keVee. We further demonstrate a position calibration method for the internal bars of the matrix using cosmic-ray muons as an alternative to emission sources that cannot easily access these bars, with an average measured resolution of 14.86+-0.29mm for depositions between 900keVee and 1000keVee. The coincident time resolution reported between pairs of bars measured up to 400ps from muon acquisitions. Energy and position calibration values measured with muons are consistent with those obtained using particle emission sources.

Two-axis crosstalk analysis of gimbal-less MEMS scanners with consideration of rotational alignment

The two-axis crosstalk of a gimbal-less Micro-Electro-Mechanical-system (MEMS) scanner was analyzed to estimate the mechanical crosstalk due to imperfect decoupling of hinged linkages and/or fabrication error. Two types of geometrical crosstalk, caused by rotational alignment angle and fan-shaped distortion, were theoretically derived, and total crosstalk was measured at two rotational alignment angles of the MEMS scanner. The mechanical crosstalk in a quasi-static mode was estimated as 0.9% by comparing the theoretical results with experimental ones based on the least squared error. The proposed method was validated for one-axis driving over a wide range of optical scan angle and extended for two-axis driving to examine the feasibility and limitation of the proposed method. The maximum discrepancy of crosstalk between theoretical calculations and experimental results was 0.72% for one-axis driving and 2.22% for two-axis driving, respectively. This method can be used to mitigate the crosstalk of MEMS scanners for enhanced performance.

Design of 2D Sparse Array Transducers for Anomaly Detection in Medical Phantoms.

Aperiodic sparse 2D ultrasonic array configurations, including random array, log spiral array, and sunflower array, have been considered for their potential as conformable transducers able to image within a focal range of 30–80 mm, at an operating frequency of 2 MHz. Optimisation of the imaging performance of potential array patterns has been undertaken based on their simulated far field directivity functions. Two evaluation criteria, peak sidelobe level (PSL) and integrated sidelobe ratio (ISLR), are used to access the performance of each array configuration. Subsequently, a log spiral array pattern with −19.33 dB PSL and 2.71 dB ISLR has been selected as the overall optimal design. Two prototype transducers with the selected log spiral array pattern have been fabricated and characterised, one using a fibre composite element composite array transducer (CECAT) structure, the other using a conventional 1–3 composite (C1–3) structure. The CECAT device demonstrates improved coupling coefficient (0.64 to 0.59), reduced mechanical cross-talk between neighbouring array elements (by 10 dB) and improved operational bandwidth (by 16.5%), while the C1–3 device performs better in terms of sensitivity (~50%). Image processing algorithms, such as Hough transform and morphological opening, have been implemented to automatically detect and dimension particles located within a fluid-filled tube structure, in a variety of experimental scenarios, including bespoke phantoms using tissue mimicking material. Experiments using the fabricated CECAT log spiral 2D array transducer demonstrated that this algorithmic approach was able to detect the walls of the tube structure and stationary anomalies within the tube with a precision of ~0.1 mm.

CAFs and Cancer Cells Co-Migration in 3D Spheroid Invasion Assay.

In many solid tumors, collective cell invasion prevails over single-cell dissemination strategies. Collective modes of invasion often display specific front/rear cellular organization, where invasive leader cells arise from cancer cell populations or the tumor stroma. Collective invasion involves coordinated cellular movements which require tight mechanical crosstalk through specific combinations of cell-cell interactions and cell-matrix adhesions.Cancer Associated Fibroblasts (CAFs) have been recently reported to drive the dissemination of epithelial cancer cells through ECM remodeling and direct intercellular contact. However, the cooperation between tumor and stromal cells remains poorly understood. Here we present a simple spheroid invasion assay to assess the role of CAFs in the collective migration of epithelial tumor cells. This method enables the characterization of 3D spheroid invasion patterns through live cell fluorescent labeling combined with spinning disc microscopy. When embedded in extracellular matrix, the invasive strands of spheroids can be tracked and leader/follower organization of CAFs and cancer cells can be quantified.