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Bats rely on their hand-wings to execute agile flight maneuvers, to grasp objects, and cradle young. Embedded in the dorsal and ventral membranes of bat wings are microscopic hairs. Past research findings implicate dorsal wing hairs in airflow sensing for flight control, but the function of ventral wing hairs has not been previously investigated. Here, we test the hypothesis that ventral wing hairs carry mechanosensory signals for flight control, prey capture, and handling. To test this hypothesis, we used synchronized high-speed stereo video and audio recordings to quantify flight and echolocation behaviors of big brown bats (Eptesicus fuscus) engaged in an aerial insect capture task. We analyzed prey-capture strategy and performance, along with flight kinematics, before and after depilation of microscopic hairs from the bat's ventral wing and tail membranes. We found that ventral wing hair depilation significantly impaired the bat's prey-capture performance. Interestingly, ventral wing hair depilation also produced increases in the bat's flight speed, an effect previously attributed exclusively to airflow sensing along the dorsal wing surface. These findings demonstrate that microscopic hairs embedded in the ventral wing and tail membranes of insectivorous bats provide mechanosensory feedback for prey handling and flight control. [ABSTRACT FROM AUTHOR]

Mechanical forces influence different cell types in our bodies. Among the earliest forces experienced in mammals is blood movement in the vascular system. Blood flow starts at the embryonic stage and ceases when the heart stops. Blood flow exposes endothelial cells (ECs) that line all blood vessels to hemodynamic forces. ECs detect these mechanical forces (mechanosensing) through mechanosensors, thus triggering physiological responses such as changes in vascular diameter. In this review, we focus on endothelial mechanosensing and on how different ion channels, receptors, and membrane structures detect forces and mediate intricate mechanotransduction responses. We further highlight that these responses often reflect collaborative efforts involving several mechanosensors and mechanotransducers. We close with a consideration of current knowledge regarding the dysregulation of endothelial mechanosensing during disease. Because hemodynamic disruptions are hallmarks of cardiovascular disease, studying endothelial mechanosensing holds great promise for advancing our understanding of vascular physiology and pathophysiology. [ABSTRACT FROM AUTHOR]

Disturbed flow promotes progression of atherosclerosis at particular regions of arteries where the recent studies show the arterial wall becomes stiffer. Objective of this study is to show how mechanotransduction in subcellular organelles of endothelial cells (ECs) will alter with changes in blood flow profiles applied on ECs surface and mechanical properties of arterial wall where ECs are attached to. We will examine the exposure of ECs to atherogenic flow profiles (disturbed flow) and non-atherogenic flow profiles (purely forward flow), while stiffness and viscoelasticity of arterial wall will change. A multicomponent model of endothelial cell monolayer was applied to quantify the response of subcellular organelles to the changes in their microenvironment. Our results show that arterial stiffening alters mechanotransduction in intra/inter-cellular organelles of ECs by slight increase in the transmitted stresses, particularly over central stress fibers (SFs). We also observed that degradation of glycocalyx and exposure to non-atherogenic flow profiles result in significantly higher stresses in subcellular organelles, while degradation of glycocalyx and exposure to atherogenic flow profiles result in dramatically lower stresses in the organelles. Moreover, we show that increasing the arterial wall viscoelasticity leads to slight increase in the stresses transmitted to subcellular organelles. FAs are particularly influenced with the changes in the arterial wall properties and viscoelasticity. Our study suggests that changes in viscoelasticity of arterial wall and degradation state of glycocalyx have to be considered along with arterial stiffening in designing more efficient treatment strategies for atherosclerosis. Our study provides insight into significant role of mechanotransduction in the localization of atherosclerosis by quantifying the role of ECs mechanosensors and suggests that mechanotransduction may play a key role in design of more efficient and precision therapeutics to slow down or block the progression of atherosclerosis. [ABSTRACT FROM AUTHOR]

Leukocytes (neutrophils, monocytes) in the active circulation exhibit multiple phenotypic indicators for a low level of cellular activity, like lack of pseudopods and minimal amounts of activated, cell-adhesive integrins on their surfaces. In contrast, before these cells enter the circulation in the bone marrow or when they recross the endothelium into extravascular tissues of peripheral organs they are fully activated. We review here a multifaceted mechanism mediated by fluid shear stress that can serve to deactivate leukocytes in the circulation. The fluid shear stress controls pseudopod formation via the FPR receptor, the same receptor responsible for pseudopod projection by localized actin polymerization. The bioactivity of macromolecular factors in the blood plasma that interfere with receptor stimulation by fluid flow, such as proteolytic cleavage in the extracellular domain of the receptor or the membrane actions of cholesterol, leads to a defective ability to respond to fluid shear stress by actin depolymerization. The cell reaction to fluid shear involves CD18 integrins, nitric oxide, cGMP and Rho GTPases, is attenuated in the presence of inflammatory mediators and modified by glucocorticoids. The mechanism is abolished in disease models (genetic hypertension and hypercholesterolemia) leading to an increased number of activated leukocytes in the circulation with enhanced microvascular resistance and cell entrapment. In addition to their role in binding to biochemical agonists/antagonists, membrane receptors appear to play a second role: to monitor local fluid shear stress levels. The fluid shear stress control of many circulating cell types such as lymphocytes, stem cells, tumor cells remains to be elucidated.

Bio‐inspired cilium‐based mechanosensors offer a high level of responsiveness, making them suitable for a wide range of industrial, environmental, and biomedical applications. Despite great promise, the development of sensors with multifunctionality, scalability, customizability, and sensing linearity presents challenges due to the complex sensing mechanisms and fabrication methods involved. To this end, high‐aspect‐ratio polycaprolactone/graphene cilia structures with high conductivity, and facile fabrication are employed to address these challenges. For these 3D‐printed structures, an "inter‐cilium contact" sensing mechanism that enables the sensor to function akin to an on‐off switch, significantly enhancing sensitivity and reducing ambiguity in detection, is proposed. The cilia structures exhibit high levels of customizability, including thickness, height, spacing, and arrangement, while maintaining mechanical robustness. The simplicity of the sensor design enables highly sensitive detection in diverse applications, encompassing airflow and water flow monitoring, braille detection, and debris recognition. Overall, the unique conductive cilia‐based sensing mechanism that is proposed brings several advantages, advancing the development of multi‐sensing capabilities and flexible electronic skin applications in smart robotics and human prosthetics. [ABSTRACT FROM AUTHOR]

The ability of skeletal muscles to sense mechanical stimuli and respond to them by changing intracellular electrochemical and biochemical processes (mechanotransduction) is of crucial importance for the regulation of physiological processes in muscle fibers. This review describes the main sarcolemmal, sarcomeric, and cytoskeletal mechanosensitive structures and analyzes mechano-dependent signaling pathways and mechanisms involved in the regulation of gene expression, as well as muscle protein synthesis and degradation. The final part of the review formulates specific questions in the field of muscle mechanotransduction that need to be addressed in future studies. The understanding of skeletal muscle mechanotransduction is required for the development of effective measures aimed at the treatment of muscular dystrophies, sarcopenia, and prevention of disuse-induced muscle atrophy. [ABSTRACT FROM AUTHOR]

Abstract Bio‐inspired cilium‐based mechanosensors offer a high level of responsiveness, making them suitable for a wide range of industrial, environmental, and biomedical applications. Despite great promise, the development of sensors with multifunctionality, scalability, customizability, and sensing linearity presents challenges due to the complex sensing mechanisms and fabrication methods involved. To this end, high‐aspect‐ratio polycaprolactone/graphene cilia structures with high conductivity, and facile fabrication are employed to address these challenges. For these 3D‐printed structures, an “inter‐cilium contact” sensing mechanism that enables the sensor to function akin to an on‐off switch, significantly enhancing sensitivity and reducing ambiguity in detection, is proposed. The cilia structures exhibit high levels of customizability, including thickness, height, spacing, and arrangement, while maintaining mechanical robustness. The simplicity of the sensor design enables highly sensitive detection in diverse applications, encompassing airflow and water flow monitoring, braille detection, and debris recognition. Overall, the unique conductive cilia‐based sensing mechanism that is proposed brings several advantages, advancing the development of multi‐sensing capabilities and flexible electronic skin applications in smart robotics and human prosthetics.

Hui Li,* Wen-Ying Zhou,* Yi-Yuan Xia,* Jun-Xia Zhang Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun-Xia Zhang, Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, People’s Republic of China, Tel +86 15366155682, Email zhangjunshia@njmu.edu.cnAbstract: Vascular endothelial cells (ECs), derived from the mesoderm, form a single layer of squamous cells that covers the inner surface of blood vessels. In addition to being regulated by chemical signals from the extracellular matrix (ECM) and blood, ECs are directly confronted to complex hemodynamic environment. These physical inputs are translated into biochemical signals, dictating multiple aspects of cell behaviour and destination, including growth, differentiation, migration, adhesion, death and survival. Mechanosensors are initial responders to changes in mechanical environments, and the overwhelming majority of them are located on the plasma membrane. Physical forces affect plasma membrane fluidity and change of protein complexes on plasma membrane, accompanied by altering intercellular connections, cell-ECM adhesion, deformation of the cytoskeleton, and consequently, transcriptional responses in shaping specific phenotypes. Among the diverse forces exerted on ECs, shear stress (SS), defined as tangential friction force exerted by blood flow, has been extensively studied, from mechanosensing to mechanotransduction, as well as corresponding phenotypes. However, the precise mechanosensors and signalling pathways that determine atheroprone and atheroprotective phenotypes of arteries remain unclear. Moreover, it is worth to mention that some established mechanosensors of atheroprotective SS, endothelial glycocalyx, for example, might be dismantled by atheroprone SS. Therefore, we provide an overview of the current knowledge on mechanosensors in ECs for SS signals. We emphasize how these ECs coordinate or differentially participate in phenotype regulation induced by atheroprone and atheroprotective SS.Keywords: shear stress, endothelial cells, mechanosensors, mechanotransduction

Mechanobiology is a domain of interdisciplinary research that aims to explore the impact of physical force, applied externally or internally, on cell and tissue function, including development, growth, and differentiation. Mechanotransduction is a term that describes how cells sense physical forces (such as compression, stretch, and shear stress), convert them into biochemical signals, and mount adaptive responses integrated by the nucleus. There is accumulating evidence that mechanical forces extensively inform the biological behaviour of liver cells in health and disease. Recent research has elucidated many cellular and molecular mechanisms involved in this process including the pleiotropic control and diverse effects of the paralogous transcription co-activators YAP/TAZ, which play a prominent role in mechanotransduction. The liver sinusoids represent a unique microenvironment in which cells are exposed to mechanical cues originating in the cytoskeleton and at interfaces with adjacent cells, the extracellular matrix, and vascular or interstitial fluids. In non-alcoholic fatty liver disease (NAFLD), hepatocellular lipid accumulation and ballooning, activation of inflammatory responses, dysfunction of liver sinusoidal endothelial cells, and transdifferentiation of hepatic stellate cells into a pro-contractile and pro-fibrotic phenotype have been associated with aberrant cycles of mechanosensing and mechanoresponses. The downstream consequences of disrupted mechanical homeostasis likely contribute to the progression of NAFLD and promote the development of portal hypertension, cirrhosis, and hepatocellular carcinoma. Identification of molecular targets involved in pathogenic mechanotransduction will allow for the development of novel strategies to prevent the progression of liver disease in NAFLD. [ABSTRACT FROM AUTHOR]

Internal mechanosensors, as the core component of a proprioceptive system, provide vital mechanical information from intelligent devices for adaptive motor control, mechanical fault diagnosis, and machining condition monitoring. However, developing a sophisticated mechanosensory structure that can be widely used is highly desirable to significantly improve the detection performance of internal mechanosensors. Coincidentally, in nature, optimized microscale slits of arachnids (e.g., scorpions and spiders) are ingeniously used as a mechanosensory structure for internal mechanosensilla to efficiently detect the inevitable internal mechanical feedbacks caused by self‐motion and external mechanical stimuli. Biological slit‐based mechano‐sensilla provide an attractive bio‐inspired strategy to use the controllable slit as the sensory structure to improve the perceptual performance of internal mechanosensors. In this study, the structure‐deformation‐performance coupling relationship of slit‐based mechano‐sensilla is explored through experiment and theoretical analysis. An artificial slit‐based mechanosensor is developed by mimicking the combined deformation properties of the slit and the ultrathin cuticular membrane covering the slit tail. This bio‐inspired mechanosensor shows excellent performance in terms of mechanical stability, response time, and sensitivity to mechanical signals. The research on a practical application highlights the importance of the unique basic "design" principles of the slit‐based mechano‐sensilla in improving the proprioceptive capability of smart engineering devices. [ABSTRACT FROM AUTHOR]

Background Lipoprotein lipase (LPL)‐derived fatty acid is a major source of energy for cardiac contraction. Synthesized in cardiomyocytes, LPL requires translocation to the vascular lumen for hydrolysis of lipoprotein triglyceride, an action mediated by endothelial cell (EC) release of heparanase. We determined whether flow‐mediated biophysical forces can cause ECs to secrete heparanase and thus regulate cardiac metabolism. Methods and Results Isolated hearts were retrogradely perfused. Confluent rat aortic ECs were exposed to laminar flow using an orbital shaker. Cathepsin L activity was determined using gelatin‐zymography. Diabetes was induced in rats with streptozotocin. Despite the abundance of enzymatically active heparanase in the heart, it was the enzymatically inactive, latent heparanase that was exceptionally responsive to flow‐induced release. EC exposed to orbital rotation exhibited a similar pattern of heparanase secretion, an effect that was reproduced by activation of the mechanosensor, Piezo1. The laminar flow‐mediated release of heparanase from EC required activation of both the purinergic receptor and protein kinase D, a kinase that assists in vesicular transport of proteins. Heparanase influenced cardiac metabolism by increasing cardiomyocyte LPL displacement along with subsequent replenishment. The flow‐induced heparanase secretion was augmented following diabetes and could explain the increased heparin‐releasable pool of LPL at the coronary lumen in these diabetic hearts. Conclusions ECs sense fluid shear‐stress and communicate this information to subjacent cardiomyocytes with the help of heparanase. This flow‐induced mechanosensing and its dynamic control of cardiac metabolism to generate ATP, using LPL‐derived fatty acid, is exquisitely adapted to respond to disease conditions, like diabetes.

Introduction—Local hemodynamics impact the mechanotransduction in endothelial cells (ECs) lining the vascular network. On the other hand, cancer cells are shown to influence the local hemodynamics in their vicinity, in microvasculature. The first objective of present study is to explore how cancer cell-induced changes in local hemodynamics can impact the forces experienced by intra/inter-cellular organelles of ECs that are believed to play important roles in mechanotransduction. Moreover, extracellular matrix (ECM) stiffening has been shown to correlate with progression of most cancer types. However, it is still not well understood how ECM stiffness impacts ECs mechanosensors. The second objective of this study is to elucidate the role of ECM stiffness on mechanotransduction in ECs. Methods—A three-dimensional, multiscale, multicomponent, viscoelastic model of focally adhered ECs is developed to simulate the force transmission through ECs mechanosensors [actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs), and adherens junctions (ADJs)]. Results—Our results show that cancer cell-altered hemodynamics results in significantly high forces transmitted to subcellular organelles of ECs which are in vicinity of cancer cells. This impact is more drastic on stress fibers (SFs) both centrally located and peripheral ones. Furthermore, we demonstrate that ADJs, FAs, and SFs experience higher stresses in ECs attached to stiffer ECM. Impact of ECM stiffness is particularly significant in ECs exposed to fluid shear stresses of 2 Pa or lower. This finding reveals the role of organ-specific stiffness in promoting cancer cell transmigration even in capillaries larger than cancer cell diameter. Conclusions—ÊCancer cell-induced-changes in ECs mechanotransduction represents an important potential mechanism for cancer cell transmigration in the microvasculature particularly with stiffer ECM. The identification of ECs mechanosensors involved in early stages of EC-cancer cell interaction will help with developing more efficient therapeutic interventions to suppress cancer cell transmigration in the microvasculature. [ABSTRACT FROM AUTHOR]

In an effort to develop the next generation of neural implants, current research has focused on solving the challenges associated with the foreign body reaction and promoting long‐term device performance in vivo. Although the cutting edge of research in this field appears to be moving away from traditional metallic and semiconductor materials, the complex tissue dynamics which occur at the electrode–neural interface following device implantation are yet to be resolved. In particular, understanding the molecular processes of gliosis and the onset and persistence of scar formation is key in developing stable and specific neural recording/stimulation devices. Critically, it is recognized that neural device implantation leads to a significant disruption of tissue integrity at the peri‐electrode site. Accordingly, an in‐depth understanding of mechanotransduction in neuronal cell populations at the peri‐implant region is required to better inform neural interface design. This perspective highlights the need for a comprehensive mechanobiological understanding of gliosis to enhance the development of neural implants with improved chronic functionality.

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer deaths globally. More than 80% of HCC patients have a background of fibrosis or cirrhosis, which leads to changes in physical factors in tumor microenvironment (TME), such as increased stiffness, solid stress, fluid stresses and structural alterations in the extracellular matrix (ECM). In the past, the focus of cancer research has predominantly been on genetic and biochemical factors in the TME, and the critical role of physical factors has often been overlooked. Recent discoveries suggest these unique physical signals are converted into biochemical signals through a mechanotransduction process that influences the biological behavior of tumor cells and stromal cells. This process facilitates the occurrence and progression of tumors. This review delves into the alterations in the mechanical microenvironment during the progression of liver fibrosis to HCC, the signaling pathways activated by physical signals, and the effects on both tumor and mesenchymal stromal cells. Furthermore, this paper summarizes and discusses the therapeutic options for targeting the mechanical aspects of the TME, offering valuable insights for future research into novel therapeutic avenues against HCC and other solid tumors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Bionic engineering provides a promising way for promoting the development of science and technology. Next‐generation diversified mechanosensors that can efficiently sense four types of mechanical signals, including tactile, vibration, air/water flow, and sound, are also benefiting from the bioinspired approach. Natural organisms have evolved sophisticated biological mechanosensilla with excellent performance, such as ultrahigh sensitivity, resolution, stability, anti‐interference, and miniaturization, providing a great deal of inspiration for urgently needed mechanosensors that are difficult to achieve through conventional methods. Here, the recent advances in biological mechanosensilla and corresponding bioinspired mechanosensors are reviewed in detail. According to the classification of the mechanosensilla, i.e., tactile sensilla, vibrational sensilla, flow sensilla, and acoustic sensilla, this review is mainly divided into four parts. In each part, the research on functional mechanisms of the mechanosensilla based on well‐organized mechanosensory micro/nanostructures and unique functional materials, as well as the bionic design strategy and preparative technique of bioinspired mechanosensors are individually summarized and discussed. Meanwhile, insight into the further efforts in comprehensive understanding of the mechanosensilla, learning from the multiperformance integration of sensilla, and establishing the efficient preparation methods for bioinspired mechanosensors is provided, all of which are needed to be addressed urgently before having bioinspired mechanosensors of practical value. [ABSTRACT FROM AUTHOR]

Pandemics caused by viruses have threatened lives of thousands of people. Understanding the complicated process of viral infection provides significantly directive implication to epidemic prevention and control. Viral infection is a complex and diverse process, and substantial studies have been complemented in exploring the biochemical and molecular interactions between viruses and hosts. However, the physical microenvironment where infections implement is often less considered, and the role of mechanobiology in viral infection remains elusive. Mechanobiology focuses on sensation, transduction, and response to intracellular and extracellular physical factors by tissues, cells, and extracellular matrix. The intracellular cytoskeleton and mechanosensors have been proven to be extensively involved in the virus life cycle. Furthermore, innovative methods based on micro- and nanofabrication techniques are being utilized to control and modulate the physical and chemical cell microenvironment, and to explore how extracellular factors including stiffness, forces, and topography regulate viral infection. Our current review covers how physical factors in the microenvironment coordinate viral infection. Moreover, we will discuss how this knowledge can be harnessed in future research on cross-fields of mechanobiology and virology.

Besides its structural properties in the nucleoskeleton, Lamin A/C is a mechanosensor protein involved in perceiving the elasticity of the extracellular matrix. In this study we provide evidence about Lamin A/C-mediated regulation of osteosarcoma cell adhesion and spreading on substrates with tissue-specific elasticities. Our working hypothesis is based on the observation that low-aggressive and bone-resident SaOS-2 osteosarcoma cells express high level of Lamin A/C in comparison to highly metastatic, preferentially to the lung, osteosarcoma 143B cells, thereby suggesting a role for Lamin A/C in tumor cell tropism. Specifically, LMNA gene over-expression in 143B cells induced a reduction in tumor cell aggressiveness in comparison to parental cells, with decreased proliferation rate and reduced migration capability. Furthermore, LMNA reintegration into 143B cells changed the adhesion properties of tumor cells, from a preferential tropism toward the 1.5 kPa PDMS substrate (resembling normal lung parenchyma) to the 28 kPa (resembling pre-mineralized bone osteoid matrix). Our study suggests that Lamin A/C expression could be involved in the organ tropism of tumor cells, thereby providing a rationale for further studies focused on the definition of cancer mechanism of metastatization.

Typically, unit discharge of slowly adapting receptors (SARs) declines slowly when lung inflation pressure is constant, although in some units it increases instead—a phenomenon hereinafter referred to as creeping. These studies characterize creeping behavior observed in 62 of 137 SAR units examined in anesthetized, open-chest, and mechanically ventilated rabbits. SAR units recorded from the cervical vagus nerve were studied during 4 s of constant lung inflation at 10, 20, and 30 cmH2O. Affected SAR units creep more quickly as inflation pressure increases. SAR units also often deactivate after creeping, i.e., their activity decreases or stops completely. Creeping likely results from encoder switching from a low discharge to a high discharge SAR, because it disappears in SAR units with multiple receptive fields after blocking a high discharge encoder in one field leaves low discharge encoders intact. The results support that encoder switching is a common mechanism operating in lung mechanosensory units. [ABSTRACT FROM AUTHOR]

This central interaction clarifies a dual sympatho-inhibitory mechanism by which carotid sinus nerve stimulation may be beneficial in patients with resistant hypertension or heart failure. Keywords: Afferent; Sympathetic; Mechanosensors; PIEZO; ASIC; Neuroimmune; Microbiome; Microneurography EN Afferent Sympathetic Mechanosensors PIEZO ASIC Neuroimmune Microbiome Microneurography 467 471 5 07/22/21 20210801 NES 210801 In reflecting on decades of autonomic research, I recall the 2009 Walter B. Cannon Memorial Award Lecture, which I entitled In Search of Autonomic Balance: The Good, The Bad and The Ugly [[1]]. We demonstrated that the resetting of the baroreceptors is predominantly neuronal rather than vascular, identified mechanosensitive ion channels in isolated patch-clamped baroreceptor neurons, and found that pulsatility of the arterial pressure signal prevents baroreceptor afferent adaptation and sustains reflex sympathoinhibition. First evolving concept: the neurosensory integration of human sympathetic activity and its cl... Hypertension, heart failure and obstructive sleep apnea are disorders with excessive sympathetic nerve activity as a major contributor to cardiovascular mortality. [Extracted from the article]

The ability to sense external mechanical stimuli is vital for all organisms. Integrins are transmembrane receptors that mediate bidirectional signalling between the extracellular matrix (ECM) and the cytoskeleton in animals. Thus, integrins can sense changes in ECM mechanics and can translate these into internal biochemical responses through different signalling pathways. In the model yeast species Saccharomyces cerevisiae there are no proteins with sequence similarity to mammalian integrins. However, we here emphasise that the WSC-type (Wsc1, Wsc2, and Wsc3) and the MID-type (Mid2 and Mtl1) mechanosensors in yeast act as partial functional integrin analogues. Various environmental cues recognised by these mechanosensors are transmitted by a conserved signal transduction cascade commonly referred to as the PKC1-SLT1 cell wall integrity (CWI) pathway. We exemplify the WSC- and MID-type mechanosensors functional analogy to integrins with a number of studies where they resemble the integrins in terms of both mechanistic and molecular features as well as in the overall phenotypic consequences of their activity. In addition, many important components in integrin-dependent signalling in humans are conserved in yeast; for example, Sla1 and Sla2 are homologous to different parts of human talin, and we propose that they together might be functionally similar to talin. We also propose that the yeast cell wall is a prominent cellular feature involved in sensing a number of external factors and subsequently activating different signalling pathways. In a hypothetical model, we propose that nutrient limitations modulate cell wall elasticity, which is sensed by the mechanosensors and results in filamentous growth. We believe that mechanosensing is a somewhat neglected aspect of yeast biology, and we argue that the physiological and molecular consequences of signal transduction initiated at the cell wall deserve more attention.

Pollen tube (PT) serves as a vehicle that delivers male gametes (sperm cells) to a female gametophyte during double fertilization, which eventually leads to the seed formation. It is one of the fastest elongating structures in plants. Normally, PTs traverse through the extracellular matrix at the transmitting tract after penetrating the stigma. While the endeavor may appear simple, the molecular processes and mechanics of the PT elongation is yet to be fully resolved. Although it is the most studied “tip–growing” structure in plants, several features of the structure (e.g., Membrane dynamics, growth behavior, mechanosensing etc.) are only partially understood. In many aspects, PTs are still considered as a tissue rather than a “unique cell.” In this review, we have attempted to discuss mainly on the mechanics behind PT–elongation and briefly on the molecular players involved in the process. Four aspects of PTs are particularly discussed: the PT as a cell, its membrane dynamics, mechanics of its elongation, and the potential mechanosensors involved in its elongation based on relevant findings in both plant and non-plant models.

Abstract Localised extracellular interactions between nanoparticles and transmembrane signal receptors may well activate cancer cell growth. Herein, tiny LaF3 and PrF3 nanoparticles in DMEM+FBS suspensions stimulated tumour cell growth in three different human cell lines (A549, SW837 and MCF7). Size distribution of nanoparticles, activation of AKT and ERK signalling pathways and viability tests pointed to mechanical stimulation of ligand adhesion binding sites of integrins and EGFR via a synergistic action of an ensemble of tiny size nanoparticles (

Embryonic boundaries were first described in Drosophila, and then in vertebrate embryos, as cellular interfaces between compartments. They display signaling properties and in vertebrates might allocate cells fated to different anatomical structures, or cells that will play different functions over time. One of the vertebrate embryonic structures with boundaries is the hindbrain, the posterior brain vesicle, which is transitory segmented upon morphogenesis. The hindbrain is formed by iterative units called rhombomeres that constitute units of gene expression and cell-lineage compartments. Rhombomeric cells are segregated by interhombomeric boundaries, which are prefigured by sharp gene expression borders. Hindbrain boundaries were first described as static groups of cells. However, later discoveries demonstrated the dynamic behavior of this specific cell population. They play distinct functional properties during brain morphogenesis that partially overlap on time, starting as a mechanical barrier to prevent cell intermingling, becoming a signaling hub, to finally constitute a group of proliferating progenitors providing differentiated neurons to the system. In this review, I try to give a more functional overview of this segmentation process and in particular of hindbrain boundaries. I will discuss the new challenges in the field on how to integrate cell fate specification and morphogenesis during brain embryonic development. [ABSTRACT FROM AUTHOR]

Pollen tube (PT) serves as a vehicle that delivers male gametes (sperm cells) to a female gametophyte during double fertilization, which eventually leads to the seed formation. It is one of the fastest elongating structures in plants. Normally, PTs traverse through the extracellular matrix at the transmitting tract after penetrating the stigma. While the endeavor may appear simple, the molecular processes and mechanics of the PT elongation is yet to be fully resolved. Although it is the most studied "tip–growing" structure in plants, several features of the structure (e.g., Membrane dynamics, growth behavior, mechanosensing etc.) are only partially understood. In many aspects, PTs are still considered as a tissue rather than a "unique cell." In this review, we have attempted to discuss mainly on the mechanics behind PT–elongation and briefly on the molecular players involved in the process. Four aspects of PTs are particularly discussed: the PT as a cell, its membrane dynamics, mechanics of its elongation, and the potential mechanosensors involved in its elongation based on relevant findings in both plant and non-plant models. [ABSTRACT FROM AUTHOR]

In the last decades, a promising breakthrough in fluorescence imaging was represented by the advent of super-resolution microscopy (SRM). Super-resolution techniques recently became a popular method to study sub-cellular structures, providing a successful approach to observe cytoskeletal and focal adhesion proteins. Among the SR techniques, single-molecule localization microscopy plays a significant role due to its ability to unveil structures and molecular organizations in biological systems. Furthermore, since they provide information at the molecular level, these techniques are increasingly being used to study the stoichiometry and interaction between several membrane channel proteins and their accessory subunits. The aim of this review is to describe the single-molecule localization-based techniques and their applications relevant to cytoskeletal structures and membrane complexes in order to provide as future prospective an overall picture of their correlation with the mechanosensor channel expression and activity. [ABSTRACT FROM AUTHOR]

The cell nucleus responds to mechanical cues with changes in size, morphology, and motility. Previous work showed that external forces couple to nuclei through the cytoskeleton network, but we show here that changes in nuclear shape can be driven solely by calcium levels. Fluid shear stress applied to MDCK cells caused the nuclei to shrink through a Ca2+ dependent signaling pathway. Inhibiting mechanosensitive Piezo1 channels with GsMTx4 prevented nuclear shrinkage. Piezo1 knockdown also significantly reduced the nuclear shrinkage. Activation of Piezo1 with the agonist Yoda1 caused similar nucleus shrinkage without shear stress. These results demonstrate that Piezo1 channel is a key element for transmitting shear force input to nuclei. To ascertain the relative contributions of Ca2+ to cytoskeleton perturbation, we examined the F-actin reorganization under shear stress and static conditions, and showed that reorganization of the cytoskeleton is not necessary for nuclear shrinkage. These results emphasize the role of the mechanosensitive channels as primary transducers in force transmission to the nucleus. [ABSTRACT FROM AUTHOR]

Aim: The aim was to determine the role of aging and exercise training on endothelial mechanosensor proteins and the hyperemic response to shear stress by passive leg movement.Methods: We examined the expression of mechanosensor proteins and vascular function in young (n = 14, 25 ± 3 years) and old (n = 14, 72 ± 5 years) healthy male subjects with eight weeks of aerobic exercise training. Before and after training, the hyperaemic response to passive leg movement was determined and a thigh muscle biopsy was obtained before and after passive leg movement to assess the acute effect of increased shear stress. Biopsies were analyzed for protein amount and phosphorylation of mechanosensor proteins; Platelet endothelial cell adhesion molecule-1 (PECAM-1), Vascular endothelial cadherin, Vascular endothelial growth factor receptor-2 and endothelial nitric oxide synthase (eNOS).Results: Before training, the old group presented a lower hyperaemic response to passive leg movement and a 35% lower (P < 0.05) relative basal phosphorylation level of PECAM-1 whereas there was no difference for the other mechanosensor proteins. After training, the eNOS protein amount, the amount of PECAM-1 protein and the passive leg movement-induced phosphorylation of PECAM-1 were higher in both groups. The hyperaemic response to passive leg movement was higher after training in the young group only.Conclusion: Aged individuals have a lower hyperaemic response to passive leg movement and a lower relative basal phosphorylation of PECAM-1 than young. The higher PECAM-1 phosphorylation despite a similar hyperemic level in the aged observed after training, suggests that training improved shear stress responsiveness of this mechanotransduction protein.

The variable effects of mechanical stimuli induced by exercise on the human body are becoming better understood. Additionally, the indispensable effect of constant gravity on the human body to construct and maintain living organisms is known from observed muscle and bone regression induced by long-term recumbency or visits to gravity-free environments, such as space. Based on reactions of the body, cells faced with various inputs largely depend on gene expression, biochemical processes, or both. Thus, it is easy to imagine that physical input can be converted into a chemical process. The conversion process that changes physical forces (mechanical stimuli) into chemical reactions in a cell is called mechanotransduction. A growing number of studies examining mechanotransduction have led to a new phase in the understanding of exercise-induced effects on organisms.

Aim: The aim was to determine the role of aging and exercise training on endothelial mechanosensor proteins and the hyperemic response to shear stress by passive leg movement. Methods: We examined the expression of mechanosensor proteins and vascular function in young (n = 14, 25 ± 3 years) and old (n = 14, 72 ± 5 years) healthy male subjects with eight weeks of aerobic exercise training. Before and after training, the hyperaemic response to passive leg movement was determined and a thigh muscle biopsy was obtained before and after passive leg movement to assess the acute effect of increased shear stress. Biopsies were analyzed for protein amount and phosphorylation of mechanosensor proteins; Platelet endothelial cell adhesion molecule-1 (PECAM-1), Vascular endothelial cadherin, Vascular endothelial growth factor receptor-2 and endothelial nitric oxide synthase (eNOS). Results: Before training, the old group presented a lower hyperaemic response to passive leg movement and a 35% lower (P < 0.05) relative basal phosphorylation level of PECAM-1 whereas there was no difference for the other mechanosensor proteins. After training, the eNOS protein amount, the amount of PECAM-1 protein and the passive leg movement-induced phosphorylation of PECAM-1 were higher in both groups. The hyperaemic response to passive leg movement was higher after training in the young group only. Conclusion: Aged individuals have a lower hyperaemic response to passive leg movement and a lower relative basal phosphorylation of PECAM-1 than young. The higher PECAM-1 phosphorylation despite a similar hyperemic level in the aged observed after training, suggests that training improved shear stress responsiveness of this mechanotransduction protein. [ABSTRACT FROM AUTHOR]

Abstract: Lately, the growing body of quantitative data has provided evidence of the importance of mechanical forces in embryogenesis. The study of spatial and temporal distribution of mechanical tension in the course of embryogenesis is one of the most important problems of modern developmental biology. Development of genetically encoded fluorescent mechanosensors allowed their application in an intravital study of mechanical tension in developing embryos via noninvasive techniques. The possibility of applying fluorescent mechanosensors based on vinculin and C-cadherin to visualize mechanical tension in tissues of Gallus and Xenopus embryos was studied. The methods to express and detect these proteins, as well as process the resulting images, were elaborated. The best results were obtained using Xenopus embryos and the vinculin-based mechanosensor. [ABSTRACT FROM AUTHOR]

Membrane regulatory proteins, such as CD46, CD55, and CD59, prevent excess complement activation and to protect cells from damage. Previous investigations confirmed that shear stress in the physiological range was more favorable for endothelial progenitor cells (EPCs) to repair injured vascular endothelial cells and operates mainly in atheroprotective actions. However, detailed events that contribute to shear stress-induced protection in EPCs, particularly the mechanisms of signal transduction, remain poorly understood. In this study, we observed shear stress-mediated changes in the expression of complement regulatory proteins CD46, CD55, and CD59 on human EPCs and focused on the mechanical transmission mechanism in transformed cells in response to the ECM-F-actin pathway in vitro. Shear stress was observed to promote the expression of complement regulatory protein CD59, but not CD46 or CD55, on EPCs. In addition, the shear stress-induced CD59 expression was confirmed to be associated with the ECM components and was alleviated in EPCs pretreated with GRGDSP, which inhibits ECM components-integrin interaction. Furthermore, shear stress also promotes the rearrangement and polymerization of F-actin. However, shear stress-induced CD59 expression was reduced when the F-actin stress fiber formation process was delayed by Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) or destroyed by cytochalasin D (Cyto D), while Jasplakinolide (JAS) reversed the expression of CD59 through promotion of F-actin polymerization and its stabilizing capacities. Our results indicates that shear stress is an important mediator in EPC expression of CD59 regulated by the ECM-F-actin pathway, which is a key factor in preventing membrane attack complex (MAC) -mediated cell autolysis. [ABSTRACT FROM AUTHOR]

Two conventional doctrines govern airway mechanosensory interpretation: One-Sensor Theory (OST) and Line-Labeled Theory (LLT). In OST, one afferent fiber connects to a single sensor. In LLT, a different type of sensor sends signals via its specific line to a particular brain region to evoke its reflex. Thus, airway slowly adapting receptors (SARs) inhibit breathing and rapidly adapting receptors (RARs) stimulate breathing. However, recent studies show many different mechanosensors connect to a single afferent fiber (Multiple-Sensor Theory, MST). That is, SARs and RARs may send different types of information through the same afferent pathway, indicating different information has been integrated at the sensory unit level. Thus, a sensory unit is not merely a transducer (textbook concept), but also a processor. MST is a conceptual shift. Data generated over last eight decades under OST require re-interpretation. • Airway mechanosensors play an important role in respiratory control and other body function. • Recent research advances a paradigm shifting multiple-sensor theory to explain the mechanosensory function. • It overviews derivation of MST. • MST provides new data interpretation; for instance, coughs can arise from activating four sensor types together in the unit. [ABSTRACT FROM AUTHOR]

Mechanosensing and subsequent mechanotransduction are indispensable for muscle plasticity. Nevertheless, a scarcity of literature exists regarding an all-encompassing understanding of the muscle mechanosensing machinery's response to prolonged loading, especially in conditions that resemble a natural physiological state of skeletal muscle. This study aimed to comprehensively explore the effects of prolonged mechanical loading on mechanosensitive components, skeletal muscle characteristics, and metabolism-related gene clusters. Twenty male C57BL/6J mice were randomly divided into two groups: control and prolonged mechanical loading. To induce prolonged mechanical loading on the triceps brachii (TRI) and biceps brachii (BIC) muscles, a 14-day period of tail suspension was implemented. In TRI only, prolonged mechanical loading caused a mild fast-to-slow fiber type shift together with increased mechanosensor gene and protein levels. It also increased transcription factors associated with slow muscle fibers while decreasing those related to fast-type muscle gene expression. Succinate dehydrogenase activity, a marker of muscle oxidative capacity, and genes involved in oxidative and mitochondrial turnover increased, whereas glycolytic-related genes decreased. Moreover, prolonged mechanical loading stimulated markers of muscle protein synthesis. Taken together, our data show a collective muscle-specific increase in mechanosensor gene and protein levels upon a period of prolonged mechanical loading in conditions that reflect a more natural physiological state of skeletal muscle in mice. We provide additional proof-of-concept that prolonged tail suspension-induced loading of the forelimbs triggers a muscle-specific fast-to-slow fiber type switch, and this coincides with increased protein synthesis-related signaling. NEW & NOTEWORTHY This study provides a comprehensive overview of the effects of prolonged loading on mechanosensitive components in conditions that better reflect the natural physiological state of skeletal muscle. Although the muscle mechanosensing machinery has been widely acknowledged for its responsiveness to altered loading, an inclusive understanding of its response to prolonged loading remains scarce. Our results show a fast-to-slow fiber type shift and an upregulation of mechanosensor gene and protein levels following prolonged loading.

Summary Cells recognize and respond to changes in intra- and extracellular mechanical conditions to maintain their mechanical homeostasis. Linear contractile bundles of actin filaments and myosin II known as stress fibres (SFs) mediate mechanical signals. Mechanical cues such as excessive stress driven by myosin II and/or external force may damage SFs and induce the local transient accumulation of SF-repair complexes (zyxin and VASP) at the damaged sites. Using an atomic force microscope mounted on a fluorescence microscope, we applied mechanical damage to cells expressing fluorescently tagged cytoskeletal proteins and recorded the subsequent mobilization of SF-repair complexes. We found that a LIM protein, paxillin, transiently accumulated at the damaged sites earlier than zyxin, while paxillin knockdown did not affect the kinetics of zyxin translocation. The C-terminal half of paxillin, comprising four-tandem LIM domains, can still translocate to damaged sites on SFs, suggesting that the LIM domain is essential for the mechanosensory function of paxillin. Our findings demonstrate a crucial role of the LIM domain in mechanosensing LIM proteins.

The fruit fly Drosophila melanogaster has provided important insights into how sensory information is transduced by transient receptor potential (TRP) channels in the peripheral nervous system (PNS). However, TRP channels alone have not been able to completely model mechanosensitive transduction in mechanoreceptive chordotonal neurons (CNs). Here, we show that, in addition to TRP channels, the sole voltage-gated sodium channel (Na V ) in Drosophila , Para, is localized to the dendrites of CNs. Para is localized to the distal tip of the dendrites in all CNs, from embryos to adults, and is colocalized with the mechanosensitive TRP channels No mechanoreceptor potential C (NompC) and Inactive/Nanchung (Iav/Nan). Para localization also demarcates spike initiation zones (SIZs) in axons and the dendritic localization of Para is indicative of a likely dendritic SIZ in fly CNs. Para is not present in the dendrites of other peripheral sensory neurons. In both multipolar and bipolar neurons in the PNS, Para is present in a proximal region of the axon, comparable to the axonal initial segment (AIS) in vertebrates, 40-60 μm from the soma in multipolar neurons and 20-40 μm in bipolar neurons. Whole-cell reduction of para expression using RNAi in CNs of the adult Johnston's organ (JO) severely affects sound-evoked potentials (SEPs). However, the duality of Para localization in the CN dendrites and axons identifies a need to develop resources to study compartment-specific roles of proteins that will enable us to better understand Para's role in mechanosensitive transduction., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Ravenscroft et al.)

Physical forces affect both the function and phenotype of cells in the lung. Bronchial, alveolar, and other parenchymal cells, as well as fibroblasts and macrophages, are normally subjected to a variety of passive and active mechanical forces associated with lung inflation and vascular perfusion as a result of the dynamic nature of lung function. These forces include changes in stress (force per unit area) or strain (any forced change in length in relation to the initial length) and shear stress (the stress component parallel to a given surface). The responses of cells to mechanical forces are the result of the cell's ability to sense and transduce these stimuli into intracellular signaling pathways able to communicate the information to its interior. This review will focus on the modulation of intracellular pathways by lung mechanical forces and the intercellular signaling. A better understanding of the mechanisms by which lung cells transduce physical forces into biochemical and biological signals is of key importance for identifying targets for the treatment and prevention of physical force-related disorders.

Mollusk larvae have a stable, velum-up orientation that may influence how they sense and react to hydrodynamic signals applied in different directions. Directional sensing abilities and responses could affect how a larva interacts with anisotropic fluid motions, including those in feeding currents and in boundary layers encountered during settlement. Oyster larvae (Crassostrea virginica) were exposed to simple shear in a Couette device and to solid-body rotation in a single rotating cylinder. Both devices were operated in two different orientations, one with the axis of rotation parallel to the gravity vector, and one with the axis perpendicular. Larvae and flow were observed simultaneously with near-infrared particle-image velocimetry, and behavior was quantified as a response to strain rate, vorticity and centripetal acceleration. Only flows rotating about a horizontal axis elicited the diving response observed previously for oyster larvae in turbulence. The results provide strong evidence that the turbulence-sensing mechanism relies on gravity-detecting organs (statocysts) rather than mechanosensors (cilia). Flow sensing with statocysts sets oyster larvae apart from zooplankters such as copepods and protists that use external mechanosensors in sensing spatial velocity gradients generated by prey or predators. Sensing flow-induced changes in orientation, rather than flow deformation, would enable more efficient control of vertical movements. Statocysts provide larvae with a mechanism of maintaining their upward swimming when rotated by vortices and initiating dives toward the seabed in response to the strong turbulence associated with adult habitats. [ABSTRACT FROM AUTHOR]

Three signaling systems play the fundamental roles in modulating cell activities: chemical, electrical, and mechanical. While the former two are well studied, the mechanical signaling system is still elusive because of the lack of methods to measure structural forces in real time at cellular and subcellular levels. Indeed, almost all biological processes are responsive to modulation by mechanical forces that trigger dispersive downstream electrical and biochemical pathways. Communication among the three systems is essential to make cells and tissues receptive to environmental changes. Cells have evolved many sophisticated mechanisms for the generation, perception and transduction of mechanical forces, including motor proteins and mechanosensors. In this review, we introduce some background information about mechanical dynamics in live cells, including the ubiquitous mechanical activity, various types of mechanical stimuli exerted on cells and the different mechanosensors. We also summarize recent results obtained using genetically encoded FRET (fluorescence resonance energy transfer)-based force/tension sensors; a new technique used to measure mechanical forces in structural proteins. The sensors have been incorporated into many specific structural proteins and have measured the force gradients in real time within live cells, tissues, and animals. [ABSTRACT FROM AUTHOR]

Adding to previous efforts towards a better understanding of the remarkable diversity of spider mechanosensitive hair sensilla, this study examines hairs of Cupiennius salei most likely serving a proprioreceptive function. At the tibia-metatarsus joint of all walking legs, there are two opposing groups of hairs ventrally on the tibia (20 hairs) and metatarsus (75 hairs), respectively. These hairs deflect each other when the joint flexes during locomotion, reversibly interlocking by microtrichs on their hair shafts. The torque resisting the hair deflection into the direction of natural stimulation is smaller by up to two powers of ten than that for the other directions. The torsional restoring constant S of the hair suspension is about 10 Nm rad in the preferred direction, up to a hair deflection angle of 30° (mean of natural deflection angles). Joint movements were imposed in ranges and at rates measured in walking spiders and sensory action potentials recorded. Within the natural step frequencies (0.3-3 Hz) the rate of action potentials follows the velocity of hair deflection. All findings point to the morphological, mechanical, and physiological adaptedness of the joint hair sensilla to their proprioreceptive stimulation during locomotion. [ABSTRACT FROM AUTHOR]

Background: Positive end-expiratory pressure (PEEP) is commonly used in clinical settings. It is expected to affect the input from slowly adapting pulmonary stretch receptors (SARs), leading to altered cardiopulmonary functions. However, we know little about how SARs behave during PEEP application. Objectives: Our study aimed to characterize the behavior of SARs during PEEP application. Methods: We recorded single-unit activities from 18 SARs in the cervical vagus nerve and examined their response to an increase of PEEP from 3 to 10 cm H2O for 20 min in anesthetized, open-chest and mechanically ventilated rabbits. Results: The mean activity of the units increased immediately from 35.7 to 80.5 impulses per second at the fifth breath after increasing PEEP (n = 14, p < 0.001) and then gradually returned to 56.5 impulses per second at the end of 20 min of PEEP application (p < 0.001). In the meantime, peak airway pressure increased from 9.3 to 32.7 cm H2O, and then gradually returned to 29.4 cm H2O (n = 18; p < 0.05) after 20 min. The remaining four units ceased firing at 34.7 s (range 10-56 s) after their initial increased activity upon 10 cm H2O PEEP application. The unit activity resumed as the PEEP was returned to 3 cm H2O. Conclusions: High PEEP stimulates SARs and SAR activity gradually returns towards the baseline via multiple mechanisms including receptor deactivation, neural habituation and mechanical adaptation. Understanding of the sensory inputs during PEEP application will assist in developing better strategies of mechanical ventilation. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Antennal mechanosensors play a key role in control and stability of insect flight. In addition to the well-established role of antennae as airflow detectors, recent studies have indicated that the sensing of antennal vibrations by Johnston's organs also provides a mechanosensory feedback relevant for flight stabilization. However, few studies have addressed how the individual units, or scolopidia, of the Johnston's organs encode these antennal vibrations and communicate it to the brain. Here, we characterize the encoding properties of individual scolopidia from the Johnston's organs in the hawk moth, Manduca sexta, through intracellular neurophysiological recordings from axons of the scolopidial neurons. We stimulated the flagellum-pedicel joint using a custom setup that delivered mechanical stimuli of various (step, sinusoidal, frequency and amplitude sweeps) waveforms. Single units of the Johnston's organs typically displayed phaso-tonic responses to step stimuli with short (3-5 ms) latencies. Their phase-locked response to sinusoidal stimuli in the 0.1-100 Hz frequency range showed high fidelity (vector strengths>0.9). The neurons were able to encode different phases of the stimulus motion and were also extremely sensitive to small amplitude (<0.05 deg) deflections with some indication of directional tuning. In many cases, the firing frequency of the neurons varied linearly as a function of the stimulus frequency at wingbeat and double wingbeat frequencies, which may be relevant to their role in flight stabilization. Iontophoretic fills of these neurons with fluorescent dyes showed that they all projected in the antennal mechanosensory and motor center (AMMC) area of the brain. Taken together, these results showcase the speed and high sensitivity of scolopidia of the Johnston's organs, and hence their ability to encode fine antennal vibrations. [ABSTRACT FROM AUTHOR]

Endothelial cells (ECs) not only serve as a barrier between blood and extravascular space to modulate the exchange of fluid, macromolecules and cells, but also play a critical role in regulation of vascular homeostasis and adaptation under mechanical stimulus via intrinsic mechanotransduction. Recently, with the dissection of microdomains responsible for cellular responsiveness to mechanical stimulus, a lot of mechanosensing molecules (mechanosensors) and pathways have been identified in ECs. In addition, there is growing evidence that endothelial mechanosensors not only serve as key vascular gatekeepers, but also contribute to the pathogenesis of various vascular disorders. This review focuses on recent findings in endothelial mechanosensors in subcellular microdomains and their roles in regulation of physiological and pathological functions under mechanical stress. [ABSTRACT FROM AUTHOR]