Effects of Cyclic Strain at Focal Adhesions on Migration of an Osteoblast

2015 ◽  
Author(s):  
Tomohiro Fukuno ◽  
Toshihiko Shiraishi
Keyword(s):  
Magnetic Particles ◽  
Protein Structures ◽  
Focal Adhesions ◽  
Cyclic Strain ◽  
Time Lapse ◽  
Mechanical Forces ◽  
Osteoblast Cell ◽  
Frequency Range ◽  
Cellular Mechanisms ◽  
Biochemical Signals

Cells respond to not only biochemical signals but also mechanical forces, which indicates that cells have some mechanosensors that convert mechanical forces into biochemical signals. According to recent reports, one of the candidates of the mechanosensors is focal adhesions that form multi-protein structures having mechanical links between intracellular cytoskeletons and extracellular matrices. Since the cellular mechanisms of sensing and responding to the mechanical stimulations at focal adhesions have not been clarified yet, we developed a micropillar substrate embedding micron-sized magnetic particles and enabling the micropillars to be cyclically deflected by a time-varied magnetic field. Using the magnetic micropillars, here we apply cyclic strain of some frequencies to a single osteoblast cell through focal adhesions and track cell migration with time-lapse observation to understand how the cell senses and responds to cyclic strain. Our data indicate that the cell may change the direction of migration to move away from the micropillar cyclically deflected in the frequency range from 0.1 to 50 Hz.

Response of an Osteoblast to Cyclic Strain at Its Focal Adhesions Using Magnetic Micropillars

2012 ◽  
Author(s):  
Toshihiko Shiraishi ◽  
Takuya Ohara ◽  
Shin Morishita ◽  
Ryohei Takeuchi
Keyword(s):  
Magnetic Field ◽  
External Magnetic Field ◽  
Focal Adhesion ◽  
Mechanical Stimulation ◽  
Magnetic Particles ◽  
Focal Adhesions ◽  
Cyclic Strain ◽  
Osteoblast Cell ◽  
A Cell ◽  
The Difference

This paper describes a micro device which applies cyclic strain to focal adhesions of a cell. In recent years, evidence has been growing that focal adhesions act as mechanosensors of cells which convert mechanical force into biomechanical signaling. However, there are no effective micro devices which can directly apply mechanical stimulation to each focal adhesion. Here we develop a micropillar substrate embedding micron-sized magnetic particles and enabling the micropillars to be deflected by external magnetic field. The combination of long and short micropillars produces the difference of deflection between them and enables the micropillars to apply strain to a cell. The long pillars were periodically deflected at the amplitude of approximately 1.4 μm whereas most of short pillars were not deflected. Using the magnetic micropillar substrate, we observed the deformation of an osteoblast cell at its focal adhesions. The findings indicate that the present micro device can be used for investigating mechanosensing systems of a cell.

A Method for Applying High Cyclic Strain to Focal Adhesions and Measuring the Cell Response

2013 ◽  
Author(s):  
Toshihiko Shiraishi ◽  
Takuya Ohara ◽  
Shin Morishita
Keyword(s):  
Magnetic Field ◽  
External Magnetic Field ◽  
Focal Adhesion ◽  
High Frequency ◽  
Magnetic Particles ◽  
Focal Adhesions ◽  
Cyclic Strain ◽  
Osteoblast Cell ◽  
A Cell ◽  
The Difference

This paper describes a method by which broadband cyclic strain can be applied to focal adhesions of a cell. In recent years, evidence has been growing that focal adhesions act as mechanosensors of cells which convert mechanical force into biomechanical signaling. However, there are no effective methods by which mechanical stimulation with high frequency can be directly applied to each focal adhesion. Here we develop a micropillar substrate embedding micron-sized magnetic particles and enabling the micropillars to be deflected by external magnetic field. The combination of long and short micropillars produces the difference of deflection between them and enables the micropillars to apply strain to a cell. We verified that the micropillars responded to external magnetic field up to at least 25 Hz without phase difference. Using the magnetic micropillar substrate, we observed the cytoskeletal deformation of an osteoblast cell. The findings indicate that the present micro device can be used for investigating mechanosensing systems of a cell.

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.

Costameres, focal adhesions, and cardiomyocyte mechanotransduction

2005 ◽  
Vol 289 (6) ◽  
pp. H2291-H2301 ◽  
Author(s):  
Allen M. Samarel
Keyword(s):  
Growth Factor ◽  
Focal Adhesions ◽  
Growth Factor Signaling ◽  
Cellular Mechanisms ◽  
Growth And Survival ◽  
Specific Proteins ◽  
And Function ◽  
Cytoskeletal Elements ◽  
Biochemical Signals ◽  
Cellular Components

Mechanotransduction refers to the cellular mechanisms by which load-bearing cells sense physical forces, transduce the forces into biochemical signals, and generate appropriate responses leading to alterations in cellular structure and function. This process affects the beat-to-beat regulation of cardiac performance but also affects the proliferation, differentiation, growth, and survival of the cellular components that comprise the human myocardium. This review focuses on the experimental evidence indicating that the costamere and its structurally related structure the focal adhesion complex are critical cytoskeletal elements involved in cardiomyocyte mechanotransduction. Biochemical signals originating from the extracellular matrix-integrin-costameric protein complex share many common features with those signals generated by growth factor receptors. The roles of key regulatory kinases and other muscle-specific proteins involved in mechanotransduction and growth factor signaling are discussed, and issues requiring further study in this field are outlined.

scholarly journals Dysfunctional Mechanotransduction through the YAP/TAZ/Hippo Pathway as a Feature of Chronic Disease

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 151 ◽  
Author(s):  
Mathias Cobbaut ◽  
Simge Karagil ◽  
Lucrezia Bruno ◽  
Maria Del Carmen Diaz de la Loza ◽  
Francesca E Mackenzie ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Neurological Disorders ◽  
Cellular Structure ◽  
Hippo Pathway ◽  
External Environment ◽  
Disease Development ◽  
Mechanical Forces ◽  
Cellular Mechanisms ◽  
And Migration ◽  
Biochemical Signals

In order to ascertain their external environment, cells and tissues have the capability to sense and process a variety of stresses, including stretching and compression forces. These mechanical forces, as experienced by cells and tissues, are then converted into biochemical signals within the cell, leading to a number of cellular mechanisms being activated, including proliferation, differentiation and migration. If the conversion of mechanical cues into biochemical signals is perturbed in any way, then this can be potentially implicated in chronic disease development and processes such as neurological disorders, cancer and obesity. This review will focus on how the interplay between mechanotransduction, cellular structure, metabolism and signalling cascades led by the Hippo-YAP/TAZ axis can lead to a number of chronic diseases and suggest how we can target various pathways in order to design therapeutic targets for these debilitating diseases and conditions.

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 Extracellular vesicles from amyloid-β exposed cell cultures induce severe dysfunction in cortical neurons

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chiara Beretta ◽  
Elisabeth Nikitidou ◽  
Linn Streubel-Gallasch ◽  
Martin Ingelsson ◽  
Dag Sehlin ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Cortical Neurons ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Time Lapse ◽  
Cellular Mechanisms ◽  
Axonal Swelling ◽  
Tem Analysis ◽  
Neuronal Cell Bodies ◽  
Time Lapse Imaging

AbstractAlzheimer’s disease (AD) is characterized by a substantial loss of neurons and synapses throughout the brain. The exact mechanism behind the neurodegeneration is still unclear, but recent data suggests that spreading of amyloid-β (Aβ) pathology via extracellular vesicles (EVs) may contribute to disease progression. We have previously shown that an incomplete degradation of Aβ42 protofibrils by astrocytes results in the release of EVs containing neurotoxic Aβ. Here, we describe the cellular mechanisms behind EV-associated neurotoxicity in detail. EVs were isolated from untreated and Aβ42 protofibril exposed neuroglial co-cultures, consisting mainly of astrocytes. The EVs were added to cortical neurons for 2 or 4 days and the neurodegenerative processes were followed with immunocytochemistry, time-lapse imaging and transmission electron microscopy (TEM). Addition of EVs from Aβ42 protofibril exposed co-cultures resulted in synaptic loss, severe mitochondrial impairment and apoptosis. TEM analysis demonstrated that the EVs induced axonal swelling and vacuolization of the neuronal cell bodies. Interestingly, EV exposed neurons also displayed pathological lamellar bodies of cholesterol deposits in lysosomal compartments. Taken together, our data show that the secretion of EVs from Aβ exposed cells induces neuronal dysfunction in several ways, indicating a central role for EVs in the progression of Aβ-induced pathology.

Mechanobiology of bone cells

2010 ◽  
Vol 19 (03) ◽  
pp. 245-249
Author(s):  
J. Rychly
Keyword(s):  
Binding Sites ◽  
Bone Cells ◽  
Mechanical Forces ◽  
Integrin Receptors ◽  
Differentiation Markers ◽  
Bone Material ◽  
Adhesion Sites ◽  
Important Regulator ◽  
Biochemical Signals ◽  
Stimulation Of

SummaryBone mass, morphology and properties of the bone material are regulated by the functions of osteoblasts, osteocytes, and osteoclasts. These cells respond directly or indirectly to mechanical forces from the environment with the expression of differentiation markers, proliferation or release of bioactive factors. Osteocytes appear to be an important regulator for the adaptation of bone to changes in the mechanical environment. Mesenchymal stem cells which are located in bone marrow can be mechanically stimulated to differentiate into osteoblasts and chondrocytes but not to adipocytes. Integrin receptors are the principal mediators of mechanical forces and induce a signal transduction. The conversion of mechanical signals into biochemical signals is facilitated by unfolding of proteins to expose binding sites. Implant materials offer the opportunity to control the mechanical stimulation of cells by modifying the rigidity, geometry of adhesion sites, and the 3D-environment.

Invited Review: Engineering approaches to cytoskeletal mechanics

2000 ◽  
Vol 89 (5) ◽  
pp. 2085-2090 ◽  
Author(s):  
Dimitrije Stamenović ◽  
Ning Wang
Keyword(s):  
Cell Biology ◽  
Theoretical Models ◽  
Force Balance ◽  
Mechanical Forces ◽  
Cellular Functions ◽  
Cellular Mechanics ◽  
Recent Developments ◽  
Biochemical Mechanisms ◽  
Underlying Mechanisms ◽  
Biochemical Signals

An outstanding problem in cell biology is how cells sense mechanical forces and how those forces affect cellular functions. Various biophysical and biochemical mechanisms have been invoked to answer this question. A growing body of evidence indicates that the deformable cytoskeleton (CSK), an intracellular network of interconnected filamentous biopolymers, provides a physical basis for transducing mechanical signals into biochemical signals. Therefore, to understand how mechanical forces regulate cellular functions, it is important to know how cells respond to changes in the CSK force balance and to identify the underlying mechanisms that control transmission of mechanical forces throughout the CSK and bring it to equilibrium. Recent developments of new experimental techniques for measuring cell mechanical properties and novel theoretical models of cellular mechanics make it now possible to identify and quantitate the contributions of various CSK structures to the overall balance of mechanical forces in the cell. This review focuses on engineering approaches that have been used in the past two decades in studies of the mechanics of the CSK.

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