scholarly journals The relationship between force and focal complex development

2002 ◽  
Vol 159 (4) ◽  
pp. 695-705 ◽  
Author(s):  
Catherine G. Galbraith ◽  
Kenneth M. Yamada ◽  
Michael P. Sheetz
Keyword(s):  
Extracellular Matrix ◽  
Complex Formation ◽  
Focal Adhesions ◽  
Mechanical Force ◽  
Force Transmission ◽  
Integrin Receptors ◽  
Focal Complex ◽  
Complex Development ◽  
The Relationship

To adhere and migrate, cells must be capable of applying cytoskeletal force to the extracellular matrix (ECM) through integrin receptors. However, it is unclear if connections between integrins and the ECM are immediately capable of transducing cytoskeletal contraction into migration force, or whether engagement of force transmission requires maturation of the adhesion. Here, we show that initial integrin–ECM adhesions become capable of exerting migration force with the recruitment of vinculin, a marker for focal complexes, which are precursors of focal adhesions. We are able to induce the development of focal complexes by the application of mechanical force to fibronectin receptors from inside or outside the cell, and we are able to extend focal complex formation to vitronectin receptors by the removal of c-Src. These results indicate that cells use mechanical force as a signal to strengthen initial integrin–ECM adhesions into focal complexes and regulate the amount of migration force applied to individual adhesions at localized regions of the advancing lamella.

scholarly journals The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases.

1995 ◽  
Vol 131 (6) ◽  
pp. 1857-1865 ◽  
Author(s):  
N A Hotchin ◽  
A Hall
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Complex Formation ◽  
Map Kinase ◽  
Human Fibroblasts ◽  
Focal Adhesions ◽  
Small Gtpases ◽  
Wide Range ◽  
Focal Complex ◽  
Rho Family

Interaction of cells with extracellular matrix via integrin adhesion receptors plays an important role in a wide range of cellular: functions, for example cell growth, movement, and differentiation. Upon interaction with substrate, integrins cluster and associate with a variety of cytoplasmic proteins to form focal complexes and with the actin cytoskeleton. Although the intracellular signals induced by integrins are at present undefined, it is thought that they are mediated by proteins recruited to the focal complexes. It has been suggested, for example, that after recruitment to focal adhesions p125FAK can activate the ERK1/2 MAP kinase cascade. We have previously reported that members of the rho family of small GTPases can trigger the assembly of focal complexes when activated in cells. Using microinjection techniques, we have now examined the role of the extracellular matrix and of the two GTP-binding proteins, rac and rho, in the assembly of integrin complexes in both mouse and human fibroblasts. We find that the interaction of integrins with extracellular matrix alone is not sufficient to induce integrin clustering and focal complex formation. Similarly, activation of rho or rac by extracellular growth factors does not lead to focal complex formation in the absence of matrix. Focal complexes are only assembled in the presence of both matrix and functionally active members of the rho family. In agreement with this, the interaction of integrins with matrix in the absence of rho/rac activity is unable to activate the ERK1/2 kinases in Swiss 3T3 cells. In fact, ERK1/2 can be activated fully by growth factors in the absence of matrix and it seems unlikely, therefore, that the adhesion dependence of fibroblast growth is mediated through the ras/MAP kinase pathway. We conclude that extracellular matrix is not sufficient to trigger focal complex assembly and subsequent integrin-dependent signal transduction in the absence of functionally active members of the rho family of GTPases.

scholarly journals Effects of substrate stiffness and actomyosin contractility on coupling between force transmission and vinculin–paxillin recruitment at single focal adhesions

2017 ◽  
Vol 28 (14) ◽  
pp. 1901-1911 ◽  
Author(s):  
Dennis W. Zhou ◽  
Ted T. Lee ◽  
Shinuo Weng ◽  
Jianping Fu ◽  
Andrés J. García
Keyword(s):  
Residence Time ◽  
Focal Adhesions ◽  
Traction Force ◽  
Applied Force ◽  
Substrate Stiffness ◽  
Force Transmission ◽  
Actomyosin Contractility ◽  
Force Transfer ◽  
Cytoskeletal Tension ◽  
The Relationship

Focal adhesions (FAs) regulate force transfer between the cytoskeleton and ECM–integrin complexes. We previously showed that vinculin regulates force transmission at FAs. Vinculin residence time in FAs correlated with applied force, supporting a mechanosensitive model in which forces stabilize vinculin’s active conformation to promote force transfer. In the present study, we examined the relationship between traction force and vinculin–paxillin localization to single FAs in the context of substrate stiffness and actomyosin contractility. We found that vinculin and paxillin FA area did not correlate with traction force magnitudes at single FAs, and this was consistent across different ECM stiffness and cytoskeletal tension states. However, vinculin residence time at FAs varied linearly with applied force for stiff substrates, and this was disrupted on soft substrates and after contractility inhibition. In contrast, paxillin residence time at FAs was independent of local applied force and substrate stiffness. Paxillin recruitment and residence time at FAs, however, were dependent on cytoskeletal contractility on lower substrate stiffness values. Finally, substrate stiffness and cytoskeletal contractility regulated whether vinculin and paxillin turnover dynamics are correlated to each other at single FAs. This analysis sheds new insights on the coupling among force, substrate stiffness, and FA dynamics.

scholarly journals Mitochondria Tether to Focal Adhesions During Cell Migration and Regulate Their Size.

2021 ◽  
Author(s):  
Redaet Daniel ◽  
Patricia Bilodeau ◽  
Abebech Mengeta ◽  
Kimmy Yang ◽  
Jonathan M. Lee
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Motility ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Integrin Receptors ◽  
Substrate Interaction ◽  
Functional Part ◽  
Atp Generation ◽  
Contractile Forces

Abstract Focal Adhesions (FA) couple the actin cytoskeleton to the extracellular matrix through transmembrane integrin receptors. FA assembly and disassembly regulate cell migration by controlling substrate interaction and the generation of intracellular contractile forces. Here we show that FA interact with mitochondria. Mitochondria are highly dynamic organelles that are now emerging as regulators of mammalian cell motility. We find that mitochondria infiltrate the leading edge of NIH3T3 fibroblasts during migration and tether to FA there. Importantly, we find that FA interacting with mitochondria are larger than those lacking mitochondrial interaction. In addition, inhibition of mitochondrial ATP generation reduces FA size and artificial tethering of FA to mitochondria concomitantly increases their size. Taken together this suggests that mitochondrial interaction with FA is a functional part of cell migration and adhesion.

scholarly journals Actin Dynamics Associated with Focal Adhesions

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Corina Ciobanasu ◽  
Bruno Faivre ◽  
Christophe Le Clainche
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Body Force ◽  
Focal Adhesions ◽  
Stress Fibers ◽  
Actin Dynamics ◽  
Actin Assembly ◽  
Force Transmission ◽  
Cell Matrix ◽  
Cell Matrix Adhesion

Cell-matrix adhesion plays a major role during cell migration. Proteins from adhesion structures connect the extracellular matrix to the actin cytoskeleton, allowing the growing actin network to push the plasma membrane and the contractile cables (stress fibers) to pull the cell body. Force transmission to the extracellular matrix depends on several parameters including the regulation of actin dynamics in adhesion structures, the contractility of stress fibers, and the mechanosensitive response of adhesion structures. Here we highlight recent findings on the molecular mechanisms by which actin assembly is regulated in adhesion structures and the molecular basis of the mechanosensitivity of focal adhesions.

scholarly journals Dystrophin modulates focal adhesion tension and YAP-mediated mechanotransduction

2021 ◽  
Author(s):  
Maria Paz Ramirez ◽  
Michael JM Anderson ◽  
Lauren J Sundby ◽  
Anthony R Hagerty ◽  
Sophia J Wenthe ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Muscular Dystrophy ◽  
Focal Adhesion ◽  
Adhesion Force ◽  
Muscle Protein ◽  
Focal Adhesions ◽  
Becker Muscular Dystrophy ◽  
Missense Mutations ◽  
Force Transmission ◽  
Cell Membrane Stability

Dystrophin is an essential muscle protein that contributes to cell membrane stability by linking the actin cytoskeleton to the extracellular matrix. The absence or impaired function of dystrophin causes muscular dystrophy. Focal adhesions are mechanosensitive adhesion complexes that also connect the cytoskeleton to the extracellular matrix. However, the interplay between dystrophin and focal adhesion force transmission has not been investigated. Using a bioluminescent tension sensor, we measured focal adhesion tension in transgenic C2C12 myoblasts expressing wild type (WT) dystrophin, a non-pathogenic SNP (I232M), or two missense mutations associated with Duchenne (L54R), or Becker muscular dystrophy (L172H). We found that myoblasts expressing WT or nonpathogenic I232M dystrophin showed increased focal adhesion tension compared to non-transgenic myoblasts, while myoblasts expressing L54R or L172H dystrophin presented with decreased focal adhesion tension. Moreover, myoblasts expressing L54R or L172H dystrophin showed decreased YAP activation and exhibited slower and less directional migration compared to cells expressing WT or I232M dystrophin. Our results suggest that disease-causing missense mutations in dystrophin may disrupt a cellular tension sensing pathway in dystrophic skeletal muscle.

scholarly journals Mitochondria tether to Focal Adhesions during cell migration and regulate their size

2019 ◽  
Author(s):  
Redaet Daniel ◽  
Abebech Mengeta ◽  
Patricia Bilodeau ◽  
Jonathan M Lee
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Energy Production ◽  
Focal Adhesions ◽  
Leading Edge ◽  
Energy Requirements ◽  
Integrin Receptors ◽  
Cellular Energy ◽  
A Cell ◽  
Atp Generation

AbstractMitochondria are the key generators of ATP in a cell. Visually, they are highly dynamic organelles that undergo cellular fission and fusion events in response to changing cellular energy requirements. Mitochondria are now emerging as regulators of mammalian cell motility. Here we show that mitochondria infiltrate the leading edge of NIH3T3 fibroblasts during migration. At the leading edge, we find that mitochondria move to and tether to Focal Adhesions (FA). FA regulate cell migration by coupling the cytoskeleton to the Extracellular Matrix through integrin receptors. Importantly, we find that inhibition of mitochondrial ATP generation concomitantly inhibits FA size. This suggests that mitochondrial energy production regulates migration through FA control.

scholarly journals Extracellular matrix stiffness regulates force transmission pathways in multicellular ensembles of human airway smooth muscle cells

2018 ◽  
Author(s):  
Samuel R. Polio ◽  
Suzanne E Stasiak ◽  
Ramaswamy Krishnan ◽  
Harikrishnan Parameswaran
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Focal Adhesions ◽  
Critical Factor ◽  
Fluorescent Imaging ◽  
Airway Smooth Muscle Cells ◽  
Force Transmission ◽  
Transmission Pathways ◽  
Cell Ensemble ◽  
Cell Cell

AbstractFor an airway or a blood vessel to narrow, there must be a connected path that links the smooth muscle (SM) cells with each other, and transmits forces around the organ, causing it to constrict. Currently, we know very little about the mechanisms that regulate force transmission pathways in a multicellular SM ensemble. Here, we used extracellular matrix (ECM) micropatterning to study force transmission in a two-cell ensemble of SM cells. Using the two-SM cell ensemble, we demonstrate (a) that ECM stiffness acts as a switch that regulates whether SM force is transmitted through the ECM or through cell-cell connections. (b) Fluorescent imaging for adherens junctions and focal adhesions show the progressive loss of cell-cell borders and the appearance of focal adhesions with the increase in ECM stiffness (confirming our mechanical measurements). (c) At the same ECM stiffness, we show that the presence of a cell-cell border substantially decreases the overall contractility of the SM cell ensemble. Our results demonstrate that connectivity among SM cells is a critical factor to consider in the development of diseases such as asthma and hypertension.

scholarly journals Quantitative Evaluation of Osteocyte Morphology and Bone Anisotropic Extracellular Matrix in Rat Femur

2021 ◽  
Author(s):  
Takuya Ishimoto ◽  
Keita Kawahara ◽  
Aira Matsugaki ◽  
Hiroshi Kamioka ◽  
Takayoshi Nakano
Keyword(s):  
Extracellular Matrix ◽  
Longitudinal Axis ◽  
Rat Femur ◽  
Male Rat ◽  
Mechanical Stimuli ◽  
Axis Orientation ◽  
Principal Stress Direction ◽  
Mechanical Integrity ◽  
Osteocyte Lacunae ◽  
The Relationship

AbstractOsteocytes are believed to play a crucial role in mechanosensation and mechanotransduction which are important for maintenance of mechanical integrity of bone. Recent investigations have revealed that the preferential orientation of bone extracellular matrix (ECM) mainly composed of collagen fibers and apatite crystallites is one of the important determinants of bone mechanical integrity. However, the relationship between osteocytes and ECM orientation remains unclear. In this study, the association between ECM orientation and anisotropy in the osteocyte lacuno-canalicular system, which is thought to be optimized along with the mechanical stimuli, was investigated using male rat femur. The degree of ECM orientation along the femur longitudinal axis was significantly and positively correlated with the anisotropic features of the osteocyte lacunae and canaliculi. At the femur middiaphysis, there are the osteocytes with lacunae that highly aligned along the bone long axis (principal stress direction) and canaliculi that preferentially extended perpendicular to the bone long axis, and the highest degree of apatite c-axis orientation along the bone long axis was shown. Based on these data, we propose a model in which osteocytes can change their lacuno-canalicular architecture depending on the mechanical environment so that they can become more susceptible to mechanical stimuli via fluid flow in the canalicular channel.

scholarly journals Growth factor dependent changes in nanoscale architecture of focal adhesions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karin Legerstee ◽  
Tsion E. Abraham ◽  
Wiggert A. van Cappellen ◽  
Alex L. Nigg ◽  
Johan A. Slotman ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intermediate Layer ◽  
Cell Movement ◽  
Focal Adhesions ◽  
Bottom Layer ◽  
Vertical Axis ◽  
Longitudinal Distribution ◽  
Structured Illumination ◽  
Structured Illumination Microscopy ◽  
Mediate Cell

AbstractFocal adhesions (FAs) are flat elongated structures that mediate cell migration and link the cytoskeleton to the extracellular matrix. Along the vertical axis FAs were shown to be composed of three layers. We used structured illumination microscopy to examine the longitudinal distribution of four hallmark FA proteins, which we also used as markers for these layers. At the FA ends pointing towards the adherent membrane edge (heads), bottom layer protein paxillin protruded, while at the opposite ends (tails) intermediate layer protein vinculin and top layer proteins zyxin and VASP extended further. At the tail tips, only intermediate layer protein vinculin protruded. Importantly, head and tail compositions were altered during HGF-induced scattering with paxillin heads being shorter and zyxin tails longer. Additionally, FAs at protruding or retracting membrane edges had longer paxillin heads than FAs at static edges. These data suggest that redistribution of FA-proteins with respect to each other along FAs is involved in cell movement.

scholarly journals The YadA Protein of Yersinia pseudotuberculosis Mediates High-Efficiency Uptake into Human Cells under Environmental Conditions in Which Invasin Is Repressed

2002 ◽  
Vol 70 (9) ◽  
pp. 4880-4891 ◽  
Author(s):  
Julia Eitel ◽  
Petra Dersch
Keyword(s):  
Extracellular Matrix ◽  
Mammalian Cells ◽  
Yersinia Pseudotuberculosis ◽  
High Efficiency ◽  
Environmental Parameters ◽  
Infection Process ◽  
Nutrient Concentrations ◽  
Integrin Receptors ◽  
Uptake Process ◽  
High Level

ABSTRACT The YadA protein is a major adhesin of Yersinia pseudotuberculosis that promotes tight adhesion to mammalian cells by binding to extracellular matrix proteins. In this study, we first addressed the possibility of competitive interference of YadA and the major invasive factor invasin and found that expression of YadA in the presence of invasin affected neither the export nor the function of invasin in the outer membrane. Furthermore, expression of YadA promoted both bacterial adhesion and high-efficiency invasion entirely independently of invasin. Antibodies against fibronectin and β1 integrins blocked invasion, indicating that invasion occurs via extracellular-matrix-dependent bridging between YadA and the host cell β1 integrin receptors. Inhibitor studies also demonstrated that tyrosine and Ser/Thr kinases, as well as phosphatidylinositol 3-kinase, are involved in the uptake process. Further expression studies revealed that yadA is regulated in response to several environmental parameters, including temperature, ion and nutrient concentrations, and the bacterial growth phase. In complex medium, YadA production was generally repressed but could be induced by addition of Mg2+. Maximal expression of yadA was obtained in exponential-phase cells grown in minimal medium at 37°C, conditions under which the invasin gene is repressed. These results suggest that YadA of Y. pseudotuberculosis constitutes another independent high-level uptake pathway that might complement other cell entry mechanisms (e.g., invasin) at certain sites or stages during the infection process.

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