scholarly journals “An intrinsically disordered intracellular domain of PIEZO2 is required for force-from-filament activation of the channel”

2021 ◽  
Author(s):  
Clement Verkest ◽  
Irina Schaefer ◽  
Juri M. Jegelka ◽  
Timo A. Nees ◽  
Wang Na ◽  
...  
Keyword(s):  
Mechanical Stimuli ◽  
Force Transmission ◽  
Transmembrane Helices ◽  
Intrinsically Disordered ◽  
Membrane Stretch ◽  
Different Types ◽  
A Cell ◽  
Filament Activation ◽  
Transmission Pathways ◽  
Biochemical Signals

AbstractA central question in mechanobiology is how mechanical forces acting in or on a cell are transmitted to mechanically-gated PIEZO channels that convert these forces into biochemical signals. Here we show that PIEZO2 is sensitive to force-transmission via the membrane (force-from-lipids) as well as force transmission via the cytoskeleton (force-from-filament) and demonstrate that the latter requires the intracellular linker between the transmembrane helices nine and ten (IDR5). Moreover, we show that rendering PIEZO2 insensitive to force-from-filament by deleting IDR5 abolishes PIEZO2-mediated inhibition of neurite outgrowth, which relies on the detection of cellgenerated traction forces, while it only partially affects its sensitivity to cell indentation and does not at all alter its sensitivity to membrane stretch. Hence, we propose that PIEZO2 is a polymodal mechanosensor that detects different types of mechanical stimuli via different force transmission pathways, which highlights the importance of utilizing multiple complementary assays when investigating PIEZO channel function.

A Study of Mechanosensing of an Osteoblast at Focal Adhesions Under Cyclic Strain Using Magnetic Micropillars

2019 ◽  
Author(s):  
Toshihiko Shiraishi ◽  
Kota Nagai
Keyword(s):  
Calcium Ion ◽  
Mechanical Vibration ◽  
Focal Adhesions ◽  
Cyclic Strain ◽  
Mechanical Stimuli ◽  
Osteoblast Cells ◽  
Intracellular Calcium Ion ◽  
A Cell ◽  
Sense And Respond ◽  
Biochemical Signals

Abstract It has been reported that cells sense and respond to mechanical stimuli. Mechanical vibration promotes the cell proliferation and the cell differentiation of osteoblast cells at 12.5 Hz and 50 Hz, respectively. It indicates that osteoblast cells have a mechansensing system for mechanical vibration. There may be some mechanosensors and we focus on cellular focal adhesions through which mechanical and biochemical signals may be transmitted from extracellular matrices into a cell. However, it is very difficult to directly apply mechanical stimuli to focal adhesions. We developed a magnetic micropillar substrate on which micron-sized pillars are deflected according to applied magnetic field strength and focal adhesions adhering to the top surface of the pillars are given mechanical stimuli. In this paper, we focus on intracellular calcium ion as a second messenger of cellular mechanosensing and investigate the mechanosensing mechanism of an osteoblast cell at focal adhesions under cyclic strain using a magnetic micropillar substrate. The experimental results indicate that the magnetic micropillars have enough performance to response to an electric current applied to a coil in an electromagnet and to apply the cyclic strain of less than 3% to a cell. In the cyclic strain of less than 3%, the calcium response of a cell was not observed.

Mechanotransduction by the Actin Cytoskeleton: Converting Mechanical Stimuli into Biochemical Signals

2018 ◽  
Vol 47 (1) ◽  
pp. 617-631 ◽  
Author(s):  
Andrew R. Harris ◽  
Pamela Jreij ◽  
Daniel A. Fletcher
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Filaments ◽  
Binding Proteins ◽  
Shape Change ◽  
Cytoskeletal Proteins ◽  
Actin Binding ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Force Transmission ◽  
Biochemical Signals

Force transmission through the actin cytoskeleton plays a central role in cell movements, shape change, and internal organization. Dynamic reorganization of actin filaments by an array of specialized binding proteins creates biochemically and architecturally distinct structures, many of which are finely tuned to exert or resist mechanical loads. The molecular complexity of the actin cytoskeleton continues to be revealed by detailed biochemical assays, and the architectural diversity and dynamics of actin structures are being uncovered by advances in super-resolution fluorescence microscopy and electron microscopy. However, our understanding of how mechanical forces feed back on cytoskeletal architecture and actin-binding protein organization is comparatively limited. In this review, we discuss recent work investigating how mechanical forces applied to cytoskeletal proteins are transduced into biochemical signals. We explore multiple mechanisms for mechanical signal transduction, including the mechanosensitive behavior of actin-binding proteins, the effect of mechanical force on actin filament dynamics, and the influence of mechanical forces on the structure of single actin filaments. The emerging picture is one in which the actin cytoskeleton is defined not only by the set of proteins that constitute a network but also by the constant interplay of mechanical forces and biochemistry.

Glycans in scaffold design in tissue reconstruction

2021 ◽  
pp. 088391152199784
Author(s):  
Nipun Jain ◽  
Shashi Singh
Keyword(s):  
Cell Attachment ◽  
Low Cost ◽  
Growth Conditions ◽  
Downstream Signaling ◽  
Cell Carrier ◽  
Wide Range ◽  
Proliferation And Differentiation ◽  
Different Types ◽  
Tissue Reconstruction ◽  
A Cell

Development of an artificial tissue by tissue engineering is witnessed to be one of the long lasting clarified solutions for the damaged tissue function restoration. To accomplish this, a scaffold is designed as a cell carrier in which the extracellular matrix (ECM) performs a prominent task of controlling the inoculated cell’s destiny. ECM composition, topography and mechanical properties lead to different types of interactions between cells and ECM components that trigger an assortment of cellular reactions via diverse sensing mechanisms and downstream signaling pathways. The polysaccharides in the form of proteoglycans and glycoproteins yield better outcomes when included in the designed matrices. Glycosaminoglycan (GAG) chains present on proteoglycans show a wide range of operations such as sequestering of critical effector morphogens which encourage proficient nutrient contribution toward the growing stem cells for their development and endurance. In this review we discuss how the glycosylation aspects are of considerable importance in everyday housekeeping functions of a cell especially when placed in a controlled environment under ideal growth conditions. Hydrogels made from these GAG chains have been used extensively as a resorbable material that mimics the natural ECM functions for an efficient control over cell attachment, permeability, viability, proliferation, and differentiation processes. Also the incorporation of non-mammalian polysaccharides can elicit specific receptor responses which authorize the creation of numerous vigorous frameworks while prolonging the low cost and immunogenicity of the substance.

Mechanical competition alters the cellular interpretation of an endogenous genetic program

2021 ◽  
Vol 220 (11) ◽  
Author(s):  
Sourabh Bhide ◽  
Denisa Gombalova ◽  
Gregor Mönke ◽  
Johannes Stegmaier ◽  
Valentyna Zinchenko ◽  
...  
Keyword(s):  
Genetic Program ◽  
Cell Behavior ◽  
Mechanical Stimuli ◽  
Apical Constriction ◽  
Actin Reorganization ◽  
Ductile Materials ◽  
Nonlinear Mechanical ◽  
A Cell ◽  
Contractile Forces ◽  
Strain Responses

The intrinsic genetic program of a cell is not sufficient to explain all of the cell’s activities. External mechanical stimuli are increasingly recognized as determinants of cell behavior. In the epithelial folding event that constitutes the beginning of gastrulation in Drosophila, the genetic program of the future mesoderm leads to the establishment of a contractile actomyosin network that triggers apical constriction of cells and thereby tissue folding. However, some cells do not constrict but instead stretch, even though they share the same genetic program as their constricting neighbors. We show here that tissue-wide interactions force these cells to expand even when an otherwise sufficient amount of apical, active actomyosin is present. Models based on contractile forces and linear stress–strain responses do not reproduce experimental observations, but simulations in which cells behave as ductile materials with nonlinear mechanical properties do. Our models show that this behavior is a general emergent property of actomyosin networks in a supracellular context, in accordance with our experimental observations of actin reorganization within stretching cells.

Tracings of Behavior of Myoblasts Cultured Under Couette Type of Shear Flow Between Parallel Disks

2021 ◽  
Author(s):  
Shigehiro Hashimoto ◽  
Hiroki Yonezawa
Keyword(s):  
Shear Stress ◽  
Shear Flow ◽  
Rotating Disk ◽  
Time Lapse ◽  
Mechanical Stimuli ◽  
Parallel Disks ◽  
Before And After ◽  
A Cell

Abstract A cell deforms and migrates on the scaffold under mechanical stimuli in vivo. In this study, a cell with division during shear stress stimulation has been observed in vitro. Before and after division, both migration and deformation of each cell were analyzed. To make a Couette-type shear flow, the medium was sandwiched between parallel disks (the lower stationary culture-disc and the upper rotating disk) with a constant gap. The wall shear stress (1.5 Pa < τ < 2 Pa) on the surface of the lower culture plate was controlled by the rotational speed of the upper disc. Myoblasts (C2C12: mouse myoblast cell line) were used in the test. After cultivation without flow for 24 hours for adhesion of the cells to the lower disk, constant τ was applied to the cells in the incubator for 7 days. The behavior of each cell during shear was tracked by time-lapse images observed by an inverted phase contrast microscope placed in the incubator. Experimental results show that each cell tends to divide after higher activities: deformation and migration. The tendency is remarkable at the shear stress of 1.5 Pa.

scholarly journals Localized mechanical stimulation of single cells with engineered spatio-temporal profile

Lab on a Chip ◽  
2018 ◽  
Vol 18 (19) ◽  
pp. 2955-2965 ◽  
Author(s):  
M. Monticelli ◽  
D. S. Jokhun ◽  
D. Petti ◽  
G. V. Shivashankar ◽  
R. Bertacco
Keyword(s):  
Cell Culture ◽  
Mechanical Stimulation ◽  
Single Cells ◽  
Mechanical Stimuli ◽  
Temporal Profile ◽  
A Cell ◽  
Spatio Temporal ◽  
Stimulation Of

We introduce a new platform for mechanobiology based on active substrates, made of Fe-coated polymeric micropillars, capable to apply mechanical stimuli with tunable spatio-temporal profile on a cell culture.

scholarly journals Multifaceted role of tensins in cancer

2019 ◽  
Author(s):  
Abdulaziz Alfahed ◽  
Teresa P Raposo ◽  
Mohammad Ilyas
Keyword(s):  
Cancer Biology ◽  
Focal Adhesions ◽  
Adaptor Proteins ◽  
Therapeutic Strategies ◽  
Cell Behavior ◽  
Surrounding Environment ◽  
Signaling Mechanisms ◽  
Different Types ◽  
Biochemical Signals

Tensins are structural adaptor proteins localized at focal adhesions. Tensins can act as mechanosensors and participate in the transduction of biochemical signals from the extracellular matrix to the cytoskeleton, acting as an interface able to alter cell behavior in responses to changes in their surrounding environment. This review aims to provide a concise summary of the main functions of the four known tensins in cell and cancer biology, their homology and recently unveiled signaling mechanisms. We focus specifically on how tensin 4 (TNS4/Cten) may contribute to cancer both as an oncogene supporting metastasis and as tumour suppressor in different types of tissue. A better understanding of the cancer mechanistics involving tensins may provide the rationale for development of specific therapeutic strategies.

scholarly journals Design, Implementation, and Validation of a Piezoelectric Device to Study the Effects of Dynamic Mechanical Stimulation on Cell Proliferation, Migration and Morphology

Sensors ◽  
2020 ◽  
Vol 20 (7) ◽  
pp. 2155 ◽  
Author(s):  
Dahiana Mojena-Medina ◽  
Marina Martínez-Hernández ◽  
Miguel de la Fuente ◽  
Guadalupe García-Isla ◽  
Julio Posada ◽  
...  
Keyword(s):  
Mechanical Stimulation ◽  
Cell Monolayer ◽  
Mechanical Stimuli ◽  
Mechanical Parameters ◽  
Dynamic Stimuli ◽  
New Device ◽  
Dynamic Mechanical ◽  
Cell Functions ◽  
Biochemical Signals

Cell functions and behavior are regulated not only by soluble (biochemical) signals but also by biophysical and mechanical cues within the cells’ microenvironment. Thanks to the dynamical and complex cell machinery, cells are genuine and effective mechanotransducers translating mechanical stimuli into biochemical signals, which eventually alter multiple aspects of their own homeostasis. Given the dominant and classic biochemical-based views to explain biological processes, it could be challenging to elucidate the key role that mechanical parameters such as vibration, frequency, and force play in biology. Gaining a better understanding of how mechanical stimuli (and their mechanical parameters associated) affect biological outcomes relies partially on the availability of experimental tools that may allow researchers to alter mechanically the cell’s microenvironment and observe cell responses. Here, we introduce a new device to study in vitro responses of cells to dynamic mechanical stimulation using a piezoelectric membrane. Using this device, we can flexibly change the parameters of the dynamic mechanical stimulation (frequency, amplitude, and duration of the stimuli), which increases the possibility to study the cell behavior under different mechanical excitations. We report on the design and implementation of such device and the characterization of its dynamic mechanical properties. By using this device, we have performed a preliminary study on the effect of dynamic mechanical stimulation in a cell monolayer of an epidermal cell line (HaCaT) studying the effects of 1 Hz and 80 Hz excitation frequencies (in the dynamic stimuli) on HaCaT cell migration, proliferation, and morphology. Our preliminary results indicate that the response of HaCaT is dependent on the frequency of stimulation. The device is economic, easily replicated in other laboratories and can support research for a better understanding of mechanisms mediating cellular mechanotransduction.

scholarly journals Design and interpretation of cell trajectory assays

2013 ◽  
Vol 10 (88) ◽  
pp. 20130630 ◽  
Author(s):  
Lucie G. Bowden ◽  
Matthew J. Simpson ◽  
Ruth E. Baker
Keyword(s):  
Cell Biology ◽  
Time Interval ◽  
Short Time Interval ◽  
Trajectory Data ◽  
Time Intervals ◽  
Different Types ◽  
Long Time ◽  
A Cell ◽  
Cell Trajectory ◽  
Short Time

Cell trajectory data are often reported in the experimental cell biology literature to distinguish between different types of cell migration. Unfortunately, there is no accepted protocol for designing or interpreting such experiments and this makes it difficult to quantitatively compare different published datasets and to understand how changes in experimental design influence our ability to interpret different experiments. Here, we use an individual-based mathematical model to simulate the key features of a cell trajectory experiment. This shows that our ability to correctly interpret trajectory data is extremely sensitive to the geometry and timing of the experiment, the degree of motility bias and the number of experimental replicates. We show that cell trajectory experiments produce data that are most reliable when the experiment is performed in a quasi-one-dimensional geometry with a large number of identically prepared experiments conducted over a relatively short time-interval rather than a few trajectories recorded over particularly long time-intervals.

scholarly journals Targeting Mechanotransduction in Osteosarcoma: A Comparative Oncology Perspective

2020 ◽  
Vol 21 (20) ◽  
pp. 7595
Author(s):  
Anita K. Luu ◽  
Alicia M. Viloria-Petit
Keyword(s):  
Tumour Progression ◽  
Cell Signalling ◽  
Bone Tumour ◽  
Mechanical Stimuli ◽  
Current State ◽  
Organ Systems ◽  
A Cell ◽  
Canine Models ◽  
Improved Design ◽  
And Function

Mechanotransduction is the process in which cells can convert extracellular mechanical stimuli into biochemical changes within a cell. While this a normal process for physiological development and function in many organ systems, tumour cells can exploit this process to promote tumour progression. Here we summarise the current state of knowledge of mechanotransduction in osteosarcoma (OSA), the most common primary bone tumour, referencing both human and canine models and other similar mesenchymal malignancies (e.g., Ewing sarcoma). Specifically, we discuss the mechanical properties of OSA cells, the pathways that these cells utilise to respond to external mechanical cues, and mechanotransduction-targeting strategies tested in OSA so far. We point out gaps in the literature and propose avenues to address them. Understanding how the physical microenvironment influences cell signalling and behaviour will lead to the improved design of strategies to target the mechanical vulnerabilities of OSA cells.

Sign in / Sign up

Export Citation Format

Share Document