Multiscale Layered Biomechanical Model of the Pacinian Corpuscle
TL;DR: The model identifies a few generalizable features of the lamellar structure which makes it scalable for different sizes of PC with different number of lamellae and can be used for simulating a network of PCs considering their diversity for analyzing the high-frequency VT sensitivity of the human skin.
Abstract: This paper describes a multiscale analytical model of the lamellar structure and the biomechanical response of the Pacinian Corpuscle (PC). In order to analyze the contribution of the PC lamellar structure for detecting high-frequency vibrotactile (VT) stimuli covering 10 Hz to a few kHz, the model response is studied against trapezoidal and sinusoidal stimuli. The model identifies a few generalizable features of the lamellar structure which makes it scalable for different sizes of PC with different number of lamellae. The model describes the mechanical signal conditioning of the lamellar structure in terms of a recursive transfer-function, termed as the Compression-Transmittance-Transfer-Function (CTTF). The analytical results show that with the increase of the PC layer index above 15, the PC inner core (IC) relaxes within 1 ms against step compression of the outermost layer. This model also considers the mass of each PC layer to investigate its effect on the biomechanical response of the lamellar structure. The interlamellar spacing and its biomechanical properties along with the model response are validated with experimental data in the literature. The proposed model can be used for simulating a network of PCs considering their diversity for analyzing the high-frequency VT sensitivity of the human skin.
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TL;DR: This work attempts to integrate knowledge about the architecture of mechanoreceptor cells and their sensory organs with principles of cell mechanics, and considers how engulfing tissues contribute to mechanical filtering in nematodes, fruit flies, and mice.
Abstract: Organisms as diverse as microbes, roundworms, insects, and mammals detect and respond to applied force. In animals, this ability depends on ionotropic force receptors, known as mechanoelectrical transduction (MeT) channels, that are expressed by specialized mechanoreceptor cells embedded in diverse tissues and distributed throughout the body. These cells mediate hearing, touch, and proprioception and play a crucial role in regulating organ function. Here, we attempt to integrate knowledge about the architecture of mechanoreceptor cells and their sensory organs with principles of cell mechanics, and we consider how engulfing tissues contribute to mechanical filtering. We address progress in the quest to identify the proteins that form MeT channels and to understand how these channels are gated. For clarity and convenience, we focus on sensory mechanobiology in nematodes, fruit flies, and mice. These themes are emphasized: asymmetric responses to applied forces, which may reflect anisotropy of the structure and mechanics of sensory mechanoreceptor cells, and proteins that function as MeT channels, which appear to have emerged many times through evolution.
98 citations
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TL;DR: A two-stage mechanotransduction model of its near threshold Vibrotactile (VT) sensitivity valid over 10 Hz to a few kHz is described and can be extended to simulate the neural response of a group of PCs.
Abstract: Based on recent discoveries of stretch and voltage activated ion channels in the receptive area of the Pacinian Corpuscle (PC), this paper describes a two-stage mechanotransduction model of its near threshold Vibrotactile (VT) sensitivity valid over 10 Hz to a few kHz. The model is based on the nonlinear and stochastic behavior of the ion channels represented as dependent charge sources loaded with membrane impedance. It simulates the neural response of the PC considering the morphological and statistical properties of the receptor potential and action potential with the help of an adaptive relaxation pulse frequency modulator. This model also simulates the plateaus and nonmonotonic saturation of spike rate characteristics. The stochastic simulation based on the addition of mechanical and neural noise describes that the VT Sensitivity Threshold (VTST) at higher frequencies is more noise dependent. Above 800 Hz even a SNR = 150 improves the neurophysiological VTST more than 3 dBμ. In that frequency range, an absence of the entrainment threshold and a lower sensitivity index near the absolute threshold make the upper bound of the psychophysical VTST more dependent on the experimental protocol and physical set-up. This model can be extended to simulate the neural response of a group of PCs.
34 citations
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TL;DR: A multiscale finite-element model was used to model the equilibrium response of the Pacinian corpuscle, predicting decreased compressive strain with proximity to the receptor’s core, as seen experimentally by others.
Abstract: Cutaneous mechanoreceptors transduce different tactile stimuli into neural signals that produce distinct sensations of touch. The Pacinian corpuscle (PC), a cutaneous mechanoreceptor located deep within the dermis of the skin, detects high frequency vibrations that occur within its large receptive field. The PC is comprised of lamellae that surround the nerve fiber at its core. We hypothesized that a layered, anisotropic structure, embedded deep within the skin, would produce the nonlinear strain transmission and low spatial sensitivity characteristic of the PC. A multiscale finite-element model was used to model the equilibrium response of the PC to indentation. The first simulation considered an isolated PC with fiber networks aligned with the PC’s surface. The PC was subjected to a 10 μm indentation by a 250 μm diameter indenter. The multiscale model captured the nonlinear strain transmission through the PC, predicting decreased compressive strain with proximity to the receptor’s core, as seen experimentally by others. The second set of simulations considered a single PC embedded epidermally (shallow) or dermally (deep) to model the PC’s location within the skin. The embedded models were subjected to 10 μm indentations at a series of locations on the surface of the skin. Strain along the long axis of the PC was calculated after indentation to simulate stretch along the nerve fiber at the center of the PC. Receptive fields for the epidermis and dermis models were constructed by mapping the long-axis strain after indentation at each point on the surface of the skin mesh. The dermis model resulted in a larger receptive field, as the calculated strain showed less indenter location dependence than in the epidermis model.
20 citations
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TL;DR: This work combines mechanical models of the PC with an electrochemical model of peripheral nerves to simulate the tactile response of the entire system, and supports the hypothesis that PC rapid adaptation is affected by the lamellar structures without requiring neuronal adaptivity.
Abstract: The Pacinian corpuscle (PC) is a dermal mechanoreceptor that responds to high-frequency (20–1000 Hz) vibrations. The PC's structure allows transmission of vibrations through its layers (lamellae) to the centrally-located nerve fiber (neurite). This work combines mechanical models of the PC with an electrochemical model of peripheral nerves to simulate the tactile response of the entire system. A three-stage model of response to a vibratory input was developed, consisting of (1) outer core mechanics, (2) inner core mechanics, and (3) neurite electrochemistry. The model correctly predicts the band-pass nature of the PC's frequency response, showing that the PC structure can amplify oscillatory strains within its target frequency band. Specifically, strain induced by a vibratory stimulus is amplified by a factor of 8–12 from the PC surface to the neurite. Our results also support the hypothesis that PC rapid adaptation is affected by the lamellar structures without requiring neuronal adaptivity. Simulated different-sized PCs showed a shift in frequency response, suggesting that clusters of different-sized PCs could enable more nuanced tactile encoding than uniform clusters. By modeling the PC's mechano-to-neural transduction, we can begin to characterize the mechanosensation of other receptors to understand how multiple receptors interact to create our sensation of touch.
17 citations
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TL;DR: A review of papers targeting the musculoskeletal and the cardiovascular systems, and covered only a few exemplary papers targeting other organ systems, shows a research subdomain still in its infancy, where causal confirmation papers remain the most common.
Abstract: More and more frequently, computational biomechanics deals with problems where the portion of physical reality to be modeled spans over such a large range of spatial and temporal dimensions, that it is impossible to represent it as a single space-time continuum. We are forced to consider multiple space-time continua, each representing the phenomenon of interest at a characteristic space-time scale. Multiscale models describe a complex process across multiple scales, and account for how quantities transform as we move from one scale to another. This review offers a set of definitions for this emerging field, and provides a brief summary of the most recent developments on multiscale modeling in biomechanics. Of all possible perspectives, we chose that of the modeling intent, which vastly affect the nature and the structure of each research activity. To the purpose we organized all papers reviewed in three categories: 'causal confirmation,' where multiscale models are used as materializations of the causation theories; 'predictive accuracy,' where multiscale modeling is aimed to improve the predictive accuracy; and 'determination of effect,' where multiscale modeling is used to model how a change at one scale manifests in an effect at another radically different space-time scale. Consistent with how the volume of computational biomechanics research is distributed across application targets, we extensively reviewed papers targeting the musculoskeletal and the cardiovascular systems, and covered only a few exemplary papers targeting other organ systems. The review shows a research subdomain still in its infancy, where causal confirmation papers remain the most common. WIREs Syst Biol Med 2017, 9:e1375. doi: 10.1002/wsbm.1375 For further resources related to this article, please visit the WIREs website.
17 citations
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References
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TL;DR: The importance of different collagen types not only for the understanding of collagen-related diseases, but also as a basis for the therapeutical use of members of this protein family discussed in other chapters of this issue is indicated.
Abstract: The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified so far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. This review focuses on the distribution and function of various collagen types in different tissues. It introduces their basic structural subunits and points out major steps in the biosynthesis and supramolecular processing of fibrillar collagens as prototypical members of this protein family. A final outlook indicates the importance of different collagen types not only for the understanding of collagen-related diseases, but also as a basis for the therapeutical use of members of this protein family discussed in other chapters of this issue.
1,794 citations
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TL;DR: This chapter discusses Collagen and the Mechanical Properties of Bone and Calcified Cartilage, as well as biomimetic Collagen Tissues: Collagenous Tissue Engineering and Other Applications.
Abstract: Collagen: Structure and Mechanics, an Introduction.- Collagen Diversity, Synthesis and Assembly.- Collagen Fibrillar Structure and Hierarchies.- Restraining Cross-Links Responsible for the Mechanical Properties of Collagen Fibers: Natural and Artificial.- Damage and Fatigue.- Viscoelasticity, Energy Storage and Transmission and Dissipation by Extracellular Matrices in Vertebrates.- Nanoscale Deformation Mechanisms in Collagen.- Hierarchical Nanomechanics of Collagen Fibrils: Atomistic and Molecular Modeling.- Mechanical Adaptation and Tissue Remodeling.- Tendons and Ligaments: Structure, Mechanical Behavior and Biological Function.- Collagen in Arterial Walls: Biomechanical Aspects.- The Extracellular Matrix of Skeletal and Cardiac Muscle.- The Cornea and Sclera.- Collagen and the Mechanical Properties of Bone and Calcified Cartilage.- Dentin.- Genetic Collagen Diseases: Influence of Collagen Mutations on Structure and Mechanical Behavior.- Biomimetic Collagen Tissues: Collagenous Tissue Engineering and Other Applications.
729 citations
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TL;DR: In this paper, a detailed examination of highly invasive ovarian cancer cells relative to their less invasive parental cells (HEY) demonstrates that deformability is also an accurate biomarker of metastatic potential.
Abstract: The metastatic potential of cells is an important parameter in the design of optimal strategies for the personalized treatment of cancer. Using atomic force microscopy (AFM), we show, consistent with previous studies conducted in other types of epithelial cancer, that ovarian cancer cells are generally softer and display lower intrinsic variability in cell stiffness than non-malignant ovarian epithelial cells. A detailed examination of highly invasive ovarian cancer cells (HEY A8) relative to their less invasive parental cells (HEY), demonstrates that deformability is also an accurate biomarker of metastatic potential. Comparative gene expression analyses indicate that the reduced stiffness of highly metastatic HEY A8 cells is associated with actin cytoskeleton remodeling and microscopic examination of actin fiber structure in these cell lines is consistent with this prediction. Our results indicate that cell stiffness may be a useful biomarker to evaluate the relative metastatic potential of ovarian and perhaps other types of cancer cells.
549 citations
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TL;DR: Care should be taken to maintain the vascular extracellular matrix reserve and any therapeutic manipulation of the protease/inhibitor balance must be perfectly controlled, because an accumulation of abnormal extrace cellular matrix may have unforeseen adverse effects.
Abstract: The extracellular matrix provides a structural framework essential for the functional properties of vessel walls.The three dimensional organization of the extracellular matrix molecules — elastin, collagens, proteoglycans and structural glycoproteins — synthesized during fetal development — is optimal for these functions. In uninjured arteries and veins, some proteases are constitutively expressed, but through the control of their activation and/or their inhibition by inhibitors, these proteases have a very low activity and the turn-over of elastic and collagen fibers is low. During aging and during the occurrence of vascular pathologies, the balance between proteases and their inhibitors is temporally destroyed through the induction of matrix metalloproteinase gene expression, the activation of zymogens or the secretion of enzymes by inflammatory cells. Smooth muscle cells, the most numerous cells in vascular walls, have a high ability to respond to injury through their ability to synthesize extracellular matrix molecules and protease inhibitors. However, the three dimensional organization of the newly synthesized extracellular matrix is never functionally optimal. In some other pathologies — aneurysm — the injury overcomes the responsive capacity of smooth muscle cells and the quantity of extracellular matrix decreases. In conclusion, care should be taken to maintain the vascular extracellular matrix reserve and any therapeutic manipulation of the protease/inhibitor balance must be perfectly controlled, because an accumulation of abnormal extracellular matrix may have unforeseen adverse effects.
287 citations
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TL;DR: The Pacinian corpuscle has a framework of cytoplasmic lamellae arranged concentrically in the outer zone, and bilaterally in the core, and between these is an intermediate growth zone which provides a route whereby metabolites reach the active nerve ending, as well as the cells of the growth zone.
Abstract: The Pacinian corpuscle has a framework of cytoplasmic lamellae arranged concentrically in the outer zone, and bilaterally in the core. Between these is an intermediate growth zone. The inner core shows an unexpected complexity in that its component lamellae are arranged in two symmetrical groups of nested cytoplasmic sheets. Longitudinal tissue spaces form clefts separating the two groups. The perikarya of the core lamellae lie in or near the intermediate growth zone, and send arms into the clefts. The arms then branch and terminate as lamellae which interdigitate with those of neighboring cells. The single nerve fiber loses its myelin sheath just before it reaches the inner core but retains its Schwann cell cytoplasmic covering for a short additional distance. The Schwann sheath is not continuous with the lamellae of the inner core. Inside the core the fiber contains a striking circumferential palisade of radially disposed mitochondria. The fiber does not arborize. Vascular capillaries penetrate the hilar region of the corpuscle only as far as the myelinated sheath of the nerve, and they have not been seen elsewhere in the corpuscle. There is direct continuity between the clefts of the core and tissue spaces in the vicinity of the capillaries. It is likely that this provides a route whereby metabolites reach the active nerve ending, as well as the cells of the growth zone. The outer zone consists of at least 30 flattened concentric cytoplasmic lamellae separated from one another by relatively wide fluid-filled spaces. Collagenous fibrils are present, particularly on the outer surface of lamellae, and tend to be oriented circularly. The girdle of proliferating cells constituting the growth zone, which is prominent in corpuscles from young animals, is the layer from which the outer lamellae are derived. Osmotic forces probably elevate the lamellae, and maintain turgor pressure.
270 citations
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