Mechanically Activated Integrin Switch Controls α5β1 Function

  title={Mechanically Activated Integrin Switch Controls $\alpha$5$\beta$1 Function},
  author={Julie C. Friedland and Mark H. Lee and David Boettiger},
  pages={642 - 644}
The cytoskeleton, integrin-mediated adhesion, and substrate stiffness control a common set of cell functions required for development and homeostasis that are often deranged in cancer. The connection between these mechanical elements and chemical signaling processes is not known. Here, we show that α5β1 integrin switches between relaxed and tensioned states in response to myosin II–generated cytoskeletal force. Force combines with extracellular matrix stiffness to generate tension that triggers… 
Specificities of β1 integrin signaling in the control of cell adhesion and adhesive strength.
Integrin diversity brings specificity in mechanotransduction
How the expression of particular integrin subtypes affects cellular adaptation to substrate rigidity is described and the role of integrins and associated proteins in mechanotransduction is explained, focusing on their specificity in mechanosensing and force transmission.
Integrins and extracellular matrix in mechanotransduction.
  • M. Schwartz
  • Biology, Engineering
    Cold Spring Harbor perspectives in biology
  • 2010
Current knowledge about regulation of cell function by mechanical forces acting through integrin-mediated adhesions is summarized and models for mechanotransduction and sensing of environmental forces are discussed.
Integrin activation by talin, kindlin and mechanical forces
The current understanding of how talin, kindlin and mechanical forces regulate integrin affinity and avidity is discussed, and how integrin inactivators function in this framework.
Regulation of integrin-mediated adhesions.
Distinct biophysical mechanisms of focal adhesion kinase mechanoactivation by different extracellular matrix proteins
It is shown, using a genetically encoded FAK biosensor based on fluorescence resonance energy transfer, that FN-mediated FAK activation is dependent on the mechanical tension, which may expose its otherwise hidden FN synergy site to integrin α5.
Clustering of α5β1 integrins determines adhesion strength whereas αvβ3 and talin enable mechanotransduction
High matrix forces are primarily supported by clustered α5β1Integrins, while less stable links to αvβ3 integrins initiate mechanotransduction, resulting in reinforcement of integrin-cytoskeleton linkages through talin-dependent bonds.
Cyclic mechanical reinforcement of integrin-ligand interactions.


Force Required to Break α5β1Integrin-Fibronectin Bonds in Intact Adherent Cells Is Sensitive to Integrin Activation State*
A model system is developed that characterizes the functional binding characteristic for adhesion receptors as the force required to separate the integrin-ligand bond and provides a basis for analysis of the functions of signaling and cytoskeletal elements in the adhesion process.
The mechanisms and dynamics of αvβ3 integrin clustering in living cells
Fluorescence recovery after photobleaching analysis of Mn2+-induced integrin clusters revealed increased integrin turnover compared with mature focal contacts, whereas stabilization of the open conformation of the integrin ectodomain by mutagenesis reduced integrins turnover in focal contacts.
Focal adhesions as mechanosensors: a physical mechanism.
A thermodynamic model for the mechanosensitivity of FA is proposed, according to which a molecular aggregate, subjected to pulling forces, tends to grow in the direction of force application by incorporating additional molecules.
Sensing the environment: a historical perspective on integrin signal transduction
This historical perspective traces the key findings that have led to the current understanding of these important functions of integrins.
Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function
Combining antibody-mediated clustering with monovalent ligand occupancy induced accumulation of seven cytoskeletal proteins, thereby mimicking multivalent interactions with fibronectin or polyvalent peptides.
Rapid signal transduction in living cells is a unique feature of mechanotransduction
Nanometer-scale cytoskeletal deformation analyses revealed that the strong activation sites of Src by stress colocalized with large deformation sites of microtubules, suggesting that micro Tubules are essential structures for transmitting stresses to activate cytoplasmic proteins.
A novel mode for integrin-mediated signaling: tethering is required for phosphorylation of FAK Y397.
A kinetic model was established using HT1080 cells in which there was a linear relationship between the strength of adhesion, the proportion of alpha5beta1 integrin that could be chemically cross-linked, and the number of receptor-ligand bonds.