DNA origami nanotweezer as a programmable nanoligand holder: A hybrid ANM-oxDNA simulation study.

Mechanochromic soft materials that visually indicate mechanical damage are highly desirable for nondestructive testing. However, achieving effective stress transfer in low-modulus silicone-based matrices remains challenging, especially when mechanophores are merely physically blended. In this study, we report a covalently integrated spiropyran (SP2) into a silicone-based polyurethane (SiPU) network, enabling distinct mechanochromic response under tensile deformation. In contrast, its physically blended counterpart (SP1-SiPU) exhibits no color change. Through rational design of the polyurethane hard/soft segments, we obtained a SiPU matrix with balanced modulus and toughness, facilitating efficient force transduction to the covalently bonded SP2. The resulting material demonstrates a strain-dependent color transition from pale yellow to light purple at 400% strain, with UV-vis spectroscopy confirming the SP-to-MC transformation. This work highlights the essential role of chemical bonding in enabling mechanochromism in soft materials and provides a new design paradigm for real-time damage visualization in silicone-based elastomers.

Digital motor outcomes may surpass the sensitivity of clinician-reported outcomes in hereditary spastic paraplegia (HSP), particularly in cases of mild upper limb impairment and early disease stages. We thus validated a trial-ready quantitative motor (Q-Motor) assessment of rapid alternating limb movement tasks against clinician-reported, patient-focused, and performance outcomes in HSP. Exploratory single-center cross-sectional assessment in 41 patients with different HSP genotypes (age: 48 ± 14years), with speeded foot tapping, diadochokinesia, and finger tapping measured by a high-resolution force transducer. Validation comprised discrimination from 48 age- and sex-matched controls; correlations to the Spastic Paraplegia Rating Scale (SPRS; mean: 18.6 ± 9.1), Friedreich Ataxia Rating Scale- Activities of Daily Living (FARS-ADL), and Nine-Hole Peg Test (9HPT); and stratification by functional stage (FARS stage: mild/moderate/severe = ambulatory/walking aid/wheelchair). Foot tapping best discriminated patients with HSP from controls (e.g., frequency: area under the curve [AUC] = 0.94-0.96), and particularly captured HSP severity and functional impairment by measures of foot elevation and cumulative tap force (across all measures: |rhoSPRS|= 0.33-0.59; |rhoADL|= 0.35-0.56). Speed measures of diadochokinesia and finger tapping captured functional impairment (|rhoADL|= 0.32-0.60) and impaired dexterity (|rho9HPT |= 0.53-0.77) in the upper limbs of patients with HSP-even in the mild stage, and with slowed finger tapping even in patients without upper limb pyramidal signs. Foot tapping measures were most sensitive in discriminating mild-stage impairment (AUC = 0.72-0.95) and predominantly changed between mild and moderate HSP, while upper limb measures of diadochokinesia and finger tapping predominantly changed from moderate to severe HSP. Q-Motor captures motor impairment in HSP, even in the upper limbs and mild disease stages, and should be further evaluated as a possible trial outcome by longitudinal validation in genotypically stratified cohorts and mapping to patient experience.

SummaryMechanical force transduction is essential to survival, underlying biological processes as fundamental as morphogenesis, somatosensation, audition, and interoception; and driving pathologies as diverse as hypertension and cancer metastasis. Exogenous forces are translated to intracellular signals through transient changes in membrane tension which are currently not possible to directly monitorin situ. To remedy this, we have designed and validated Tension TRAAKer, a chemigenetic fluorescent membrane tension reporter for the visualization of tension induction, propagation, and dissipation in living cells. Tension TRAAKer is derived from inserting a tension-sensitive nonconductive variant of the mechanosensitive potassium ion channel TRAAK into a self-labelling HaloTag. Increasing membrane tensions effect conformational changes in the TRAAK channel that are optically monitored by a HaloTag-conjugated fluorogenic (environment-sensitive) dye. EGFP incorporation C-terminal to the HaloTag enables unambiguous tension reporting in mobile membranes via dual-color ratiometric imaging that controls for variations in sensor density. Tension TRAAKer reports membrane tension changes rapidly, reversibly, and with spatiotemporal precision—its fluorescence scaling to both stimulus magnitude and area, with consistent effect sizes observed between diverse cell types. It better distinguishes among elevated membrane tensions than do available indirect chemical reporters, with the additional advantage of being readily genetically targetable. We thus expect Tension TRAAKer to be a powerful tool for the study of membrane tension across biological systems and disease states.

Forearm support is associated with reduced upper arm muscle activity during direction-specific isometric wrist exertions in young healthy adults.

ABSTRACT The selective activation of mechanophores over non-specific backbone scission is critical for developing stress-responsive materials, yet a unified framework integrating molecular parameters remains elusive. Here, we systematically optimize cinnamate dimer mechanophores through the concerted modulation of three orthogonal structural dimensions: regiochemical attachment topology, electronic substituent effects, and scaffold rigidity. Using solution-state ultrasonication, NMR, UV-vis, GPC, and CoGEF calculations, we decouple the contributions of these parameters to activation efficiency. The para linkage minimizes geometric misalignment, enabling efficient force transduction. Electron-donating substituents stabilize the diradical intermediate, enabling a 2.3-fold variation in rate constants compared with its electron-withdrawing counterpart. Scaffold rigidity minimizes dissipative energy losses, with the biphenyl unit providing sufficient rigidity for near-optimal transduction. The orthogonal integration of these three dimensions enables continuous programming of activation extent from ~30% to 80% under identical sonication. This work establishes a molecular-level design paradigm for engineering cyclobutane-based mechanophores with programmable force thresholds.

Vascular endothelial cells respond to environmental forces to remodel vessels during development and to achieve homeostasis, and mis-regulated responses lead to vascular dysfunction and disease. The nucleus participates in force transduction to cell-matrix junctions via the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that resides in the nuclear envelope, but how these forces are regulated and relayed is incompletely understood. We found that the LINC complex protein SUN2 is required for proper endothelial cell-matrix interactions that occur far from the nucleus and affect angiogenic expansion, vascular responses to flow, and barrier integrity. Endothelial cells lacking SUN2 had inappropriate flow responses and reduced expression of flow-mediated transcription factors in vitro and in vivo. Expression of several matrix and adhesion genes was reduced in SUN2-depleted cells, leading to defective extracellular matrix, dysmorphic focal adhesions resistant to dynamic turnover, and disturbed cell-matrix force distribution. Mechanistically, nuclear SUN2 affected dynamic regulation of the microtubule cytoskeleton that correlated with matrix metalloprotease-dependent barrier dysfunction. These findings indicate that nuclear SUN2 establishes and maintains blood vessel homeostasis by controlling microtubule-mediated effects on focal adhesion turnover and extracellular matrix properties, with implications for cardiovascular aging and diseases such as Marfan syndrome that affect vessel wall integrity.

Muscles undergo stretch-shortening cycles (SSCs) and following active stretching, work, and power during shortening are amplified compared with pure shortening contractions (i.e., SSC effect). We investigated the effects of immobilization on SSCs and the contribution of residual force depression (rFD) and enhancement (rFE). Single muscle fibres (n = 120) were chemically permeabilized from the rat soleus and medial gastrocnemius of control and cast (14days unilateral immobilization). Fibres were maximally activated while mounted between a force transducer and length controller. For SSCs, fibres were actively lengthened from sarcomere lengths of 2.5-to-3.0µm and immediately shortened back to 2.5µm (all 0.6Lo/s), work and power during shortening was compared to a shortening contraction not preceded by active lengthening. rFD and rFE were assessed using active shortening (3.0-to-2.5µm) or lengthening (2.5-to-3.0µm) contractions, respectively, both 0.6Lo/s, with steady-state isometric force compared to a fixed-end isometric contraction at the same length. Cast fibres had smaller cross-sectional areas compared to control (both P < 0.05). Compared to control fibres, cast soleus showed ~ 6% greater rFD% (P = 0.0027) but no difference in rFE% (P = 0.55), whereas cast medial gastrocnemius showed ~ 5% reduced rFE% (P = 0.001) and unaffected rFD% (P = 0.09). Cast fibres demonstrated SSC performance enhancement (~ 120% and ~ 210%, all P < 0.001), however, the enhancement was less in the cast compared to control medial gastrocnemius (~ 88% vs ~ 120%, P = 0.022), while the soleus was not (both P > 0.86). Across muscles the SSC effect mitigated deficits in absolute work and power in the cast compared to control. Therefore, SSCs can mitigate contractile deficits at the cellular level after immobilization.

Cells mechanically interface with their surroundings through the actin cytoskeleton, a network of dynamic actin filaments, force-generating myosin motor proteins, and hundreds of associated binding proteins. The cytoskeleton plays a central role in the capacity of cells to sense and respond to physical forces and the mechanical properties of their environments (mechanosensing). Mechanosensing is essential for development and tissue homeostasis, and it is frequently disrupted in hereditary developmental disorders and cancers. Mechanistic studies of cytoskeletal mechanosensing have uncovered mechanically regulated binding interactions between cytoskeletal proteins, as well as force-sensitive dynamics of subcellular cytoskeletal networks that emerge at the scale of hundreds to thousands of molecules. Here, we review recent efforts to decipher the biophysical and protein structural bases of cytoskeletal mechanosensing, emphasizing emerging approaches for directly visualizing active force transduction from the angstrom to micrometer scale.

Polymer mechanochemistry enables the transduction of mechanical force into chemical signals, providing a versatile approach for the design of adaptive and functional materials. Of particular interest is the mechanochemical generation of conjugated polymers, which holds significant promise for applications in electronics and sensing. However, progress in this area has been hindered by low activation yields and difficult quantification in bulk materials. Herein, we report a flex-activated mechanophore based on benzotricyclodecatriene (BTCD), which undergoes a retro-Diels-Alder reaction via a bond-bending mechanism. Upon ball milling, poly(BTCD) achieves efficient activation, simultaneously releasing the fluorescent reporter 1,4-bis(hexyloxy)naphthalene (BHN) for straightforward quantification and generating semiconducting polyacetylene. The reaction kinetics and activation efficiency show clear dependencies on the milling time and polymer molecular weight. The same flex-activation pathway can be triggered under uniaxial compression, enabling iterative activation in cross-linked networks without macroscopic fracture. By integration of built-in fluorescence reporting with mechanochromic response, this system establishes a multifunctional platform for mechanoresponsive materials. Our work provides a scalable and quantitative strategy to mechanochemically generate functional polyenes directly in bulk polymers, significantly expanding the scope of flex-activated mechanophores.

Embedding mechanophores into polymeric solids enables the design of materials that respond to mechanical stimuli, with applications in sensing, self-healing, and adaptive systems. This review summarizes modeling approaches for mechanophores in polymer solids across multiple length scales, from nanoscale quantum chemical models and mesoscale reactive molecular dynamics to macroscale continuum frameworks. We also discuss theoretical foundations such as force-modified potential energy surfaces. We then compare computational strategies to experimental insights, highlighting key findings, ranging from the roles of mechanophore geometry, chemical substituents, network architecture, and physical cross-linking in force transduction and activation. Persistent challenges in the field include capturing multiscale dynamics, local environmental effects, and heterogeneity. Advancing predictive models will accelerate mechanophore discovery and enable rational design of mechanoresponsive polymeric solids.

Biohybrid robots combining compliant synthetic support structures with biological actuators could enable future applications ranging from precision microsurgery to unmanned exploration. Machines actuated by living skeletal muscles are capable of adaptive behaviors, such as sensing and responding to environmental stimuli in real-time, offering functional advantages over non-biological actuators. However, typical skeletal muscle-powered biohybrid robots depend on 3D tissues which require large cell volumes and offer limited control of muscle fiber alignment, thus reducing efficiency of force generation and transduction. Here, we present a locomotive biohybrid robot powered by 2D monolayers, or thin films, of precisely aligned skeletal muscle fibers on a micropatterned hydrogel skeleton. We demonstrate how varying skeleton design parameters, ranging from material stiffness to microscale topology, impacts muscle fiber alignment and resultant actuation strains, generating forces 10X higher than previous 2D skeletal muscle actuators, improving untethered actuation longevity by ~4500X from < 10 minutes to > 30 days, and increasing efficiency of muscle force output (force per unit volume of muscle) by 20X as compared to 3D muscles. Utilizing our optimized design for skeletal muscle thin films, we create a multi-limbed robot composed of independent muscle-powered fins capable of on/off control and frequency-dependent speed control. With these control inputs, we achieve steered multidirectional locomotion at speeds up to 4 body lengths per minute in straight movement and 1200 degrees per minute in rotational movement, highlighting potential for such actuators to be transformed into long-lasting functional soft robots.

ABSTRACTPassive forces generated by the jaw adductor muscles and their connective tissues are thought to play a protective role in the feeding system by limiting gape to avoid hyperextension and minimize distractive forces at the temporomandibular joint. However, passive muscle forces have only been measured in individual jaw adductors of two non-primate mammals, and it is unknown how these forces translate to bite force at the occlusal surface and affect gape behaviors. We measured in vivo passive bite forces in eight adult Macaca mulatta at anterior (I1) and posterior (M1) bite points across linear gapes ranging from 15 to 50 mm. Active bite force data were collected at the anterior bite point from two of these macaques (one male, one female) using a custom-built bite force transducer across linear gapes ranging from 10 to 60 mm. We demonstrate that M. mulatta passive bite forces increase with gape and vary by bite point, with forces larger at M1 compared with I1 for both linear and angular gapes. Our experimental data and Hill-type muscle models of both active and passive forces suggest that passive bite forces are absolutely and relatively small at the occlusal surface in macaques and play a minimal role in constraining gape. These are the first empirical data on bite force passive tension in primates, and the first data to suggest that the macaque jaw adductor muscles exhibit unusually high compliance, potentially relating to selection for large gape behaviors.

Environmental temperatures influence most aspects of ectotherm biology, especially when fluctuating on daily and seasonal scales. The Alligator Snapping Turtle (Macrochelys temminckii) is a species of conservation concern inhabiting temperate latitudes in the southeastern United States. To study the effect of temperature and season on the bite performance of M. temminckii, we used a force transducer and high-speed videography to measure bite force and kinematics, including bite duration, jaw velocity and acceleration, and lunge velocity and acceleration, for 21 captive subadult M. temminckii. We also recorded bite behaviors, including willingness to gape and bite, and pre-bite aggressive displays. We conducted trials at 5°C, 15°C, and 25°C, and repeated our measurements in summer and winter. Maximum bite force varied significantly with temperature, albeit not to an extent likely to be biologically relevant. All bite kinematics varied significantly across at least one of the testing temperatures within seasons, with individuals performing maximally at 25°C. Willingness to bite was more affected by temperature than willingness to gape, with subjects requiring more provocation to gape and bite at 5°C than at higher temperatures and displaying fewer pre-bite aggressive behaviors. There was limited evidence of seasonal acclimation in bite kinematics, with higher summer temperatures yielding maximal performance, and measurements at lower temperatures varying little between seasons. Our findings support the need for rigorous standardization of temperature in studies of ectotherm performance and suggest that care must be taken in selecting the time of year in which temperature studies are conducted.

The purpose of this study was to assess whether initial pre-activation muscle length alters stretch-shortening cycle (SSC) performance enhancement in permeabilized single muscle fibres. Single fibres (n=16) from the psoas major of Sprague Dawley rats (n=6, 13-14weeks) were dissected and chemically permeabilized. Fibres were maximally activated (pCa 4.5) while mounted between a force transducer and length controller. For pre-activation at a long length, the fibre was passively stretched from 2.5 to an average sarcomere length of 3.0µm. After passive force stabilized, the fibre was activated before being rapidly shortened to 2.5µm at 10 Lo/s to detach all cross-bridges. Activation was maintained and once active force recovered the fibre underwent the SSC protocol. For pre-activation at optimal length, the fibre passively underwent the same protocol as the long length condition. However, activation only began once the fibre was returned to a sarcomere length of 2.5µm. For SSCs, fibres were stretched from sarcomere lengths of 2.5 to 3.0µm and immediately shortened back to 2.5µm at a speed of 0.6 Lo/s for both phases. The SSC effect was calculated by comparing work and power during shortening to an active shortening contraction not preceded by active lengthening. The SSC enhancement (∼55% increase; all P<0.003) was not significantly different between the two initial pre-activation muscle lengths (P>0.14). Therefore, initial pre-activation muscle length does not significantly alter the SSC effect of permeabilized single fibres as non-cross-bridges structures, such as titin, were unlikely to be differently modified by the pre-activation starting lengths.

The impact hammer, equipped with a force transducer, is a portable and practical tool for inducing measurable excitations in structural health monitoring (SHM). However, its reliability is often limited by uncontrolled factors such as swing power, angle, impact location, and operator consistency, particularly in nonlinear structures operating at low frequencies. While many researchers have avoided hammer testing by instead using better controlled drop mass systems or operational modal analysis (OMA) techniques, this study presents a new experimental modal analysis (EMA) approach that improves the accuracy of impact hammer testing: variable impulse hammer impact testing (VIHIT) using a single-input single-output (SISO) roving hammer and single fixed accelerometer. For a mode of interest, the imaginary component of the frequency response function (FRF) is evaluated at each test location using multiple impulses of varying magnitude. This output quantity exhibits an inverse power relationship with the input autopower spectral density (APSD) at the modal frequency. Evaluating the trend at a reference input APSD from sufficiently excited tests produces a very accurate mode shape for that input. For a given structure, nonlinear damping ratios vary with excitation and can be extracted using inverse FRF analysis. This method addresses variability in impact hammer testing by establishing reproducible trends for different impulse levels and test locations. Application to degraded timber beams demonstrated reductions in mode shape variability relative to conventional averaging and revealed impulse-dependent damping ratios ranging from approximately 0.02 to 0.04, highlighting the method’s ability to characterize nonlinear dynamic behavior. The result is a more accurate approach for extracting modal properties and mode shapes and characterizing nonlinear dynamic behavior using a SISO roving impact hammer system.

BackgroundVisualising magnetic nanoparticle (MNP) clusters is important for inductive moderate hyperthermia (IMH) as their formation influences mechanical force transduction and heat generation in malignant tumours. An applied inhomogeneous stationary magnetic field (ISMF) can direct the arrangement of MNP clusters and the force exerted on cancer cells. Herein, we analysed MNP cluster formation and changes in mechanical properties using digital breast tomosynthesis (DBT) and ultrasound shear wave elastography (SWE) for a breast phantom containing MCF-7 breast cancer cells under the influence of IMH with ISMF.ResultsTexture analysis of the tumour-mimicking region revealed that ISMF induced a 13% increase in fractal dimension and a twofold decrease in lacunarity of MNP clusters on DBT images, as well as a 20% decrease in lacunarity of apparent stiffness within fixed regions of interest on SWE images, as compared with non-targeted MNPs (p < 0.05). While the addition of MNPs increased the maximum temperature in the tumour-mimicking region only by 1.3 °C, it led to a 3.8-fold decrease in lacunarity and a 10% increase in fractal dimension on thermal images, as well as an 87% lower fraction of viable MCF-7 cells than IMH with ISMF (p < 0.05). We also considered the clinical relevance for breast cancer patients, given that the heat-pain threshold (~ 42 °C) is close to the temperatures observed during IMH, whereas the forces generated by ISMF remain below typical pressure-pain thresholds.ConclusionsISMF initiated a more uniform spatial distribution of MNP clusters, altering the SWE-derived apparent stiffness and temperature patterns in the tumour-mimicking region. While causing only a moderate temperature increase (< 42 °C), IMH combination with ISMF and MNPs significantly reduced MCF-7 viability, indicating the additional role of magneto-mechanical effects.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12938-026-01576-9.

Morphogenesis in early development involves complex and extreme deformations in response to intra- and intercellular forces. Zebrafish epiboly, the spreading of the blastoderm to cover and engulf the large yolk cell, is a key early event that sets the stage for the establishment of the body plan, but the way the forces driving expansion are generated and mediated is poorly understood. The enveloping layer (EVL), the thin squamous outer epithelium of the blastoderm, plays a central role. Forces generated in the yolk cell are transmitted through tight junctions to the marginal EVL cells, and then propagate through the rest of the EVL. To understand mechanisms of force generation and transduction during epiboly, we first need a mechanical model of the EVL capable of responding to such forces and undergoing the drastic deformation of epiboly. The expanding EVL more than doubles its surface area and experiences significant shear as it deforms from a thin cap at one pole to become a complete sphere, necessarily requiring extensive internal rearrangement. We constructed an agent-based model of the EVL and its response to exogenous forces using the center-based simulation framework, Tissue Forge. Our model captures the large viscoelastoplastic deformation of the EVL by cell rearrangement, and accommodates the required cell neighbor exchanges without losing mechanical integration. Features observed in living embryos, such as the straightening of the initially ragged leading edge, also emerge in the model. We identified two key components required for realistic epiboly in the model: first, a mechanism to enable tissue remodeling by cell rearrangement without tearing the tissue, and second, a negative feedback on the forces driving EVL expansion, to regulate and synchronize the advancement of the EVL margin. We discuss the implications of these findings for the behavior of living EVL and the mechanisms that drive epiboly.

Mechanochromic polymers that translate deformation into optical changes can allow the direct visualization of stress distribution and predict mechanical failure. Designing functional spacers for covalently integrated mechanophores can affect both mechanical performance and optical signaling; however, this is seldom addressed systematically in the literature. Here, we prepared a polymeric perylene bisimide (PBI) macromechanophore bearing poly(ϵ‐caprolactone) spacers and terminal hydroxy functionalities (M‐PBI), and covalently incorporated it into maleic anhydride‐grafted styrene‐ethylene‐butylene‐styrene (SEBS‐g‐MAH) and linear low‐density polyethylene (LLDPE‐g‐MAH). The optical, mechanical, and thermal properties of the films were benchmarked against an analogous short‐spacer PBI (P‐PBI) and a physically blended PBI (S‐PBI). We found that covalent incorporation promoted aggregate emission (640–660 nm), and, under deformation, films comprising M‐PBI and P‐PBI showed strain‐induced disaggregation, whereas S‐PBI blends remained nonmechanochromic. Notably, the incorporation of the macromechanophore M‐PBI yielded crosslinked films without compromising the mechanical properties of the polymeric matrices significantly, whereas the use of short‐chain P‐PBI crosslinker could trigger premature failure in semicrystalline LLDPE at higher loadings. Overall, this study suggests that long, compliant spacers improve force transduction and mechanochromic robustness, enabling reversible optical strain indicators in technologically relevant plastics without affecting their mechanical behavior.

Abstract Through this work we introduce the design, development and implementation of a mechanosensitive 3D-printed jaw for a uniaxial gripper system, with an integrated sensor printed monolithically with the jaw. For many mechanical systems, accurately incorporating effects of transmission issues like stiction, dead-zone, backlash into their model presents a complex challenge. Inaccurate modeling can lead to overshoot or premature arrest in systems like screw-driven grippers. To address this, we developed a 3D-printed compliant jaw incorporating a parallelogram mechanism to maintain object orientation during grasp, while permitting a controlled deformation. Although introducing compliance improves the tolerance for force-control, the use of easily deformable bodies also necessitates reliable force estimation during operation, motivating the integration of a sensor element within the mechanism itself. The directional compliance of the jaws provides a natural means of force transduction and was leveraged by printing one blade of the mechanism with a conductive piezoresistive filament, enabling the jaw to directly estimate the grasp force. The study thus focuses only on verifying the jaw's real-time force estimation performance against a reference force sensor. A linear model was selected for its ease of implementation, low computational costs and calibration simplicity. Six 20-cycle tests were conducted at varying force set-points, with the first five cycles of each test used for real-time calibration of the gauge factor. The jaw achieved reliable sensing within a 15 - 30N range, with a mean estimation error of approximately 2.6N (~11.96% of measured peak force), demonstrating the feasibility of integrating a conductive structural element into robotic gripper jaws for practical robotic grasping.