Substrate Dependence of Mechanical Response of Neurons and Astrocytes

2011 ◽  
Author(s):  
Kristin B. Bernick ◽  
Simona Socrate
Keyword(s):  
Mechanical Properties ◽  
Mechanical Response ◽  
Imaging Techniques ◽  
Cell Types ◽  
Confocal Imaging ◽  
Cell Stiffness ◽  
Large Strains ◽  
Neural Cells ◽  
Mechanical Stimuli

The response of neural cells to mechanical cues is a critical component of the innate neuroprotective cascade aimed at minimizing the consequences of traumatic brain injury (TBI). Reactive gliosis and the formation of glial scars around the lesion site are among the processes triggered by TBI where mechanical stimuli play a central role. It is well established that the mechanical properties of the microenvironment influence phenotype and morphology in most cell types. It has been shown that astrocytes change morphology [1] and cytoskeletal content [2] when grown on substrates of varying stiffness, and that mechanically injured astrocyte cultures show alterations in cell stiffness [3]. Accurate estimates of the mechanical properties of central nervous system (CNS) cells in their in-vivo conditions are needed to develop multiscale models of TBI. Lu et al found astrocytes to be softer than neurons under small deformations [4]. In recent studies, we investigated the response of neurons to large strains and at different loading rates in order to develop single cell models capable of simulating cell deformations in regimes relevant for TBI conditions [5]. However, these studies have been conducted on cells cultured on hard substrates, and the measured cell properties might differ from their in-vivo counterparts due to the aforementioned effects. Here, in order to investigate the effects of substrate stiffness on the cell mechanical properties, we used atomic force microscopy (AFM) and confocal imaging techniques to characterize the response of primary neurons and astrocytes cultured on polyacrylamide (PAA) gels of varying composition. The use of artificial gels minimizes confounding effects associated with biopolymer gels (both protein-based and polysaccharide-based) where specific receptor bindings may trigger additional biochemical responses [1].

Control of dorsoventral pattern in vertebrate neural development: induction and polarizing properties of the floor plate

Development ◽  
1991 ◽  
Vol 113 (Supplement_2) ◽  
pp. 105-122 ◽  
Author(s):  
Marysia Placzek ◽  
Toshiya Yamada ◽  
Marc Tessier-Lavigne ◽  
Thomas Jessell ◽  
Jane Dodd
Keyword(s):  
Neural Tube ◽  
Neural Development ◽  
Cell Types ◽  
Floor Plate ◽  
Neural Cells ◽  
Dorsoventral Patterning ◽  
Cellular Mechanisms ◽  
Cell Position

Distinct classes of neural cells differentiate at specific locations within the embryonic vertebrate nervous system. To define the cellular mechanisms that control the identity and pattern of neural cells we have used a combination of functional assays and antigenic markers to examine the differentiation of cells in the developing spinal cord and hindbrain in vivo and in vitro. Our results suggest that a critical step in the dorsoventral patterning of the embryonic CNS is the differentiation of a specialized group of midline neural cells, termed the floor plate, in response to local inductive signals from the underlying notochord. The floor plate and notochord appear to control the pattern of cell types that appear along the dorsoventral axis of the neural tube. The fate of neuroepithelial cells in the ventral neural tube may be defined by cell position with respect to the ventral midline and controlled by polarizing signals that originate from the floor plate and notochord.

Magnetic Resonance Elastography for the Measurement of Annulus Fibrosus Material Properties

2011 ◽  
Author(s):  
Daniel H. Cortes ◽  
Lachlan J. Smith ◽  
Sung M. Moon ◽  
Jeremy F. Magland ◽  
Alexander C. Wright ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Magnetic Resonance ◽  
Shear Modulus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Pulse Sequence ◽  
Imaging Techniques ◽  
Mechanical Vibration ◽  
Magnetic Resonance Elastography

Intervertebral disc degeneration is characterized by a progressive cascade of structural, biochemical and biomechanical changes affecting the annulus fibrosus (AF), nucleus pulposus (NP) and end plates (EP). These changes are considered to contribute to the onset of back pain. It has been shown that mechanical properties of the AF and NP change significantly with degeneration [1,2]. Therefore, mechanical properties have the potential to serve as a biomarker for diagnosis of disc degeneration. Currently, disc degeneration is diagnosed based on the detection of structural and compositional changes using MRI, X-ray, discography and other imaging techniques. These methods, however, do not measure directly the mechanical properties of the extracellular matrix of the disc. Magnetic Resonance Elastography (MRE) is a technique that has been used to measure in vivo mechanical properties of soft tissue by applying a mechanical vibration and measuring displacements with a motion-sensitized MRI pulse sequence [3]. The mechanical properties (e.g., the shear modulus) are calculated from the displacement field using an inverse method. Since the applied displacements are in the order of few microns, fibers may not be stretched enough to remove crimping. Therefore, it is unknown if the anisotropy of the AF due to the contribution of the fibers is detectable using MRE. The objective of this study is twofold: to measure shear properties of AF in different orientations to determine the degree of AF anisotropy observable by MRE, and to identify the contribution of different AF constituents to the measured shear modulus by applying different biochemical treatments.

scholarly journals Renal cell markers: lighthouses for managing renal diseases

2021 ◽  
Author(s):  
Shivangi Agarwal ◽  
Yashwanth R Sudhini ◽  
Onur K Polat ◽  
Jochen Reiser ◽  
Mehmet Mete Altintas
Keyword(s):  
High Efficiency ◽  
Imaging Techniques ◽  
Unmet Need ◽  
Cell Types ◽  
Whole Body ◽  
Renal Diseases ◽  
Cell Type ◽  
Cell Markers ◽  
Urine Production

Kidneys, one of the vital organs in our body, are responsible for maintaining whole-body homeostasis. The complexity of renal function (e.g., filtration, reabsorption, fluid and electrolyte regulation, urine production) demands diversity not only at the level of cell types but also in their overall distribution and structural framework within the kidney. To gain an in-depth molecular-level understanding of the renal system, it is imperative to discern the components of kidney and the types of cells residing in each of the sub-regions. Recent developments in labeling, tracing, and imaging techniques enabled us to mark, monitor and identify these cells in vivo with high efficiency in a minimally invasive manner. In this review, we have summarized different cell types, specific markers that are uniquely associated with those cell types, and their distribution in kidney, which altogether make kidneys so special and different. Cellular sorting based on the presence of certain proteins on the cell surface allowed for assignment of multiple markers for each cell type. However, different studies using different techniques have found contradictions in the cell-type specific markers. Thus, the term "cell marker" might be imprecise and sub-optimal, leading to uncertainty when interpreting the data. Therefore, we strongly believe that there is an unmet need to define the best cell markers for a cell type. Although, the compendium of renal-selective marker proteins presented in this review is a resource that may be useful to the researchers, we acknowledge that the list may not be necessarily exhaustive.

scholarly journals Myosin IIA interacts with the spectrin-actin membrane skeleton to control red blood cell membrane curvature and deformability

2018 ◽  
Vol 115 (19) ◽  
pp. E4377-E4385 ◽  
Author(s):  
Alyson S. Smith ◽  
Roberta B. Nowak ◽  
Sitong Zhou ◽  
Michael Giannetto ◽  
David S. Gokhin ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Motor Activity ◽  
Control Cell ◽  
Cell Types ◽  
Membrane Skeleton ◽  
Membrane Curvature ◽  
General Function ◽  
Actin Networks ◽  
Cell Shapes

The biconcave disk shape and deformability of mammalian RBCs rely on the membrane skeleton, a viscoelastic network of short, membrane-associated actin filaments (F-actin) cross-linked by long, flexible spectrin tetramers. Nonmuscle myosin II (NMII) motors exert force on diverse F-actin networks to control cell shapes, but a function for NMII contractility in the 2D spectrin–F-actin network of RBCs has not been tested. Here, we show that RBCs contain membrane skeleton-associated NMIIA puncta, identified as bipolar filaments by superresolution fluorescence microscopy. MgATP disrupts NMIIA association with the membrane skeleton, consistent with NMIIA motor domains binding to membrane skeleton F-actin and contributing to membrane mechanical properties. In addition, the phosphorylation of the RBC NMIIA heavy and light chains in vivo indicates active regulation of NMIIA motor activity and filament assembly, while reduced heavy chain phosphorylation of membrane skeleton-associated NMIIA indicates assembly of stable filaments at the membrane. Treatment of RBCs with blebbistatin, an inhibitor of NMII motor activity, decreases the number of NMIIA filaments associated with the membrane and enhances local, nanoscale membrane oscillations, suggesting decreased membrane tension. Blebbistatin-treated RBCs also exhibit elongated shapes, loss of membrane curvature, and enhanced deformability, indicating a role for NMIIA contractility in promoting membrane stiffness and maintaining RBC biconcave disk cell shape. As structures similar to the RBC membrane skeleton exist in many metazoan cell types, these data demonstrate a general function for NMII in controlling specialized membrane morphology and mechanical properties through contractile interactions with short F-actin in spectrin–F-actin networks.

scholarly journals Living myocardial slices: a novel multicellular model for cardiac translational research

2019 ◽  
Vol 41 (25) ◽  
pp. 2405-2408 ◽  
Author(s):  
Filippo Perbellini ◽  
Thomas Thum
Keyword(s):  
Translational Research ◽  
Cardiac Tissue ◽  
Heart Function ◽  
Cell Types ◽  
Human Model ◽  
Mechanical Stimuli ◽  
Cardiovascular Research ◽  
Functional Changes

Abstract Heart function relies on the interplay of several specialized cell types and a precisely regulated network of chemical and mechanical stimuli. Over the last few decades, this complexity has often been undervalued and progress in translational cardiovascular research has been significantly hindered by the lack of appropriate research models. The data collected are often oversimplified and these make the translation of results from the laboratory to clinical trials challenging and occasionally misleading. Living myocardial slices are ultrathin (100–400μm) sections of living cardiac tissue that maintain the native multicellularity, architecture, and structure of the heart and can provide information at a cellular/subcellular level. They overcome most of the limitations that affect other in vitro models and they can be prepared from human specimens, proving a clinically relevant multicellular human model for translational cardiovascular research. The publication of a reproducible protocol, and the rapid progress in methodological and technological discoveries which prevent significant structural and functional changes associated with chronic in vitro culture, has overcome the last barrier for the in vitro use of this human multicellular preparations. This technology can bridge the gap between in vitro and in vivo human studies and has the potential to revolutionize translational research approaches.

In-Vivo Mechanical Properties of Soft Tissue Covering Bony Prominences

1978 ◽  
Vol 100 (4) ◽  
pp. 194-201 ◽  
Author(s):  
J. C. Ziegert ◽  
J. L. Lewis
Keyword(s):  
Mechanical Properties ◽  
Soft Tissue ◽  
Dynamic Loading ◽  
Static Loading ◽  
Mechanical Response ◽  
Bony Prominence ◽  
Soft Tissue Covering

In order to measure in-vivo bone accelerations, it is necessary to know the mechanical response of the soft tissue covering areas of bony prominence when a load is applied through a rigid contactor. Two methods are presented for determining this response in vivo. The first method is for quasi-static loading and the second method is for dynamic loading at approximately 2000 Hz. Results are presented for various subjects and contactor geometries.

scholarly journals Inhibition of anandamide hydrolysis attenuates nociceptor sensitization in a murine model of chemotherapy-induced peripheral neuropathy

2015 ◽  
Vol 113 (5) ◽  
pp. 1501-1510 ◽  
Author(s):  
Megan L. Uhelski ◽  
Iryna A. Khasabova ◽  
Donald A. Simone
Keyword(s):  
Peripheral Neuropathy ◽  
Spontaneous Activity ◽  
Mechanical Response ◽  
Fatty Acid Amide Hydrolase ◽  
Acid Amide ◽  
Mechanical Stimuli ◽  
Painful Neuropathy ◽  
Platinum Based Chemotherapy ◽  
C Fiber

Painful neuropathy frequently develops as a consequence of commonly used chemotherapy agents for cancer treatment and is often a dose-limiting side effect. Currently available analgesic treatments are often ineffective on pain induced by neurotoxicity. Although peripheral administration of cannabinoids, endocannabinoids, and inhibitors of endocannabinoid hydrolysis has been effective in reducing hyperalgesia in models of peripheral neuropathy, including chemotherapy-induced peripheral neuropathy (CIPN), few studies have examined cannabinoid effects on responses of nociceptors in vivo. In this study we determined whether inhibition of fatty acid amide hydrolase (FAAH), which slows the breakdown of the endocannabinoid anandamide (AEA), reduced sensitization of nociceptors produced by chemotherapy. Over the course of a week of daily treatments, mice treated with the platinum-based chemotherapy agent cisplatin developed robust mechanical allodynia that coincided with sensitization of cutaneous C-fiber nociceptors as indicated by the development of spontaneous activity and increased responses to mechanical stimulation. Administration of the FAAH inhibitor URB597 into the receptive field of sensitized C-fiber nociceptors decreased spontaneous activity, increased mechanical response thresholds, and decreased evoked responses to mechanical stimuli. Cotreatment with CB1 (AM281) or CB2 (AM630) receptor antagonists showed that the effect of URB597 was mediated primarily by CB1 receptors. These changes following URB597 were associated with an increase in the endocannabinoid anandamide in the skin. Our results suggest that enhanced signaling in the peripheral endocannabinoid system could be utilized to reduce nociceptor sensitization and pain associated with CIPN.

scholarly journals Neuromesodermal progenitor origin of trunk neural crest in vivo

2021 ◽  
Author(s):  
Martyna Lukoseviciute ◽  
Sarah Mayes ◽  
Tatjana Sauka-Spengler
Keyword(s):  
Neural Crest ◽  
Single Cell Analysis ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neural Cells ◽  
Embryonic Cells ◽  
Cell Fates ◽  
Trunk Neural Crest ◽  
Bona Fide

AbstractNeural crest (NC) is a vertebrate-specific population of multipotent embryonic cells predisposed to particular derivatives along the anteroposterior (A-P) axis. While only cranial NC progenitors give rise to ectomesenchymal cell types, trunk NC is biased for neuronal cell fates. By integrating multimodal single-cell analysis we uncovered heterogenous NC cells across the entire A-P axis expressing NC regulator foxd3. We pinpointed to its specific cranial and trunk auto-regulated enhancers. The trunk foxd3 enhancer, however, did not mark the bona fide NC, but bipotent tailbud neuromesodermal progenitors (NMps). A subset of these NMp-derived pro-neural cells appeared to give rise to neuronal trunk NC in amniotes in vivo, suggesting that at least a portion of trunk NC progenitors with a bias for neuronal fates originated from NMps in vivo.

Corrigendum to: Elastic properties of the forisome

2007 ◽  
Vol 34 (11) ◽  
pp. 1053
Author(s):  
Stephen A. Warmann ◽  
William F. Pickard ◽  
Amy Q. Shen
Keyword(s):  
Mechanical Properties ◽  
Radial Direction ◽  
Mechanical Response ◽  
Viscoelastic Model ◽  
Strain Curve ◽  
Longitudinal Direction ◽  
Tensile Tests ◽  
Before And After

Forisomes are elongate Ca2+-responsive contractile protein bodies and act as flow blocking gates within the phloem of legumes. Because an understanding of their mechanical properties in vitro underpins understanding of their physiology in vivo, we undertook, using a microcantilever method, microscopic tensile tests (incremental stress-relaxation measurements) on forisomes from Canavalia gladiata (Jacq.) DC Akanata Mame and Vicia faba L. Witkiem Major. Viscoelastic properties of forisomes in their longitudinal direction were investigated before and after Ca2+-induced contraction, but in the radial direction only before contraction. Forisomes showed mechanical properties typical of a biological material with a unidirectional fibrous structure, i.e. the modulus of elasticity in the direction of their fibers is much greater than in the radial direction. Creep data were collected in all tensile tests and fit with a three parameter viscoelastic model. The pre-contraction longitudinal elastic moduli of the forisomes were not differentiable between the two species (V. faba, 660���360�kPa; C. gladiata, 600���360�kPa). Both species showed a direction-dependent mechanical response: the elastic modulus was dramatically smaller in the radial direction than in the longitudinal direction, suggesting a weak protein cross-linking amongst longitudinal protein fibers. Activation of forisomes decreased forisome stiffness longitudinally, as evidenced by the loss of toe-region in the stress strain curve, suggesting that the forisome may have dispersed or disordered its protein structure in a controlled fashion. Contractile forces generated by single forisomes undergoing activation were also measured for V. faba (510���390�nN) and C. gladiata (570���310�nN).

Elastic properties of the forisome

2007 ◽  
Vol 34 (10) ◽  
pp. 935 ◽  
Author(s):  
Stephen A. Warmann ◽  
William F. Pickard ◽  
Amy Q. Shen
Keyword(s):  
Mechanical Properties ◽  
Radial Direction ◽  
Mechanical Response ◽  
Viscoelastic Model ◽  
Strain Curve ◽  
Longitudinal Direction ◽  
Tensile Tests ◽  
Before And After

Forisomes are elongate Ca2+-responsive contractile protein bodies and act as flow blocking gates within the phloem of legumes. Because an understanding of their mechanical properties in vitro underpins understanding of their physiology in vivo, we undertook, using a microcantilever method, microscopic tensile tests (incremental stress-relaxation measurements) on forisomes from Canavalia gladiata (Jacq.) DC Akanata Mame and Vicia faba L. Witkiem Major. Viscoelastic properties of forisomes in their longitudinal direction were investigated before and after Ca2+-induced contraction, but in the radial direction only before contraction. Forisomes showed mechanical properties typical of a biological material with a unidirectional fibrous structure, i.e. the modulus of elasticity in the direction of their fibers is much greater than in the radial direction. Creep data were collected in all tensile tests and fit with a three parameter viscoelastic model. The pre-contraction longitudinal elastic moduli of the forisomes were not differentiable between the two species (V. faba, 660 ± 360 kPa; C. gladiata, 600 ± 360 kPa). Both species showed a direction-dependent mechanical response: the elastic modulus was dramatically smaller in the radial direction than in the longitudinal direction, suggesting a weak protein cross-linking amongst longitudinal protein fibers. Activation of forisomes decreased forisome stiffness longitudinally, as evidenced by the loss of toe-region in the stress strain curve, suggesting that the forisome may have dispersed or disordered its protein structure in a controlled fashion. Contractile forces generated by single forisomes undergoing activation were also measured for V. faba (510 ± 390 nN) and C. gladiata (570 ± 310 nN).

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