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Updated: May 19, 2026
07:55
Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads
Published on: March 8, 2017
Spatial-temporal reorganization of activated integrins
Cheng-han Yu1, Weiwei Luo, Michael P Sheetz
1Mechanobiology Institute, National University of Singapore, Singapore.
Cell Adhesion & Migration
|August 7, 2012
Summary
Integrin receptors initiate cell adhesion and metastasis. This study reveals sequential biophysical events in integrin activation, including long-range cluster translocation, crucial for cell spreading and mechanobiological signaling.
Area of Science:
- Cell biology
- Biophysics
- Biochemistry
Background:
- Integrin receptors mediate cell adhesion and are crucial in tumor metastasis.
- Integrin activation is regulated by mechanical cues and biochemical ligation.
- Oligomerization of activated integrins initiates cytoskeletal remodeling and downstream signaling, but their spatio-temporal dynamics are unclear.
Purpose of the Study:
- To summarize recent discoveries on the sequential biophysical events of integrin activation during early adhesion formation.
- To investigate the spatio-temporal reorganization of activated integrins and associated proteins.
- To explore the role of integrin clustering in mechanobiological activities.
Main Methods:
- Utilized cyclic Arg-Gly-Asp (RGD) peptides as mobile ligands on supported lipid membranes.
- Observed integrin αvβ3 clustering and cell spreading dynamics.
- Analyzed localized actin polymerization and recruitment of adaptor proteins.
Main Results:
- Identified previously unreported events in integrin activation, including long-range lateral translocation of integrin clusters.
- Demonstrated localized actin polymerization dependent on Src family kinases following initial integrin clustering.
- Showcased integrin clusters as reaction cores for mechanobiological activities, recruiting various adaptor proteins.
Conclusions:
- Integrin activation involves a sequence of biophysical events, including cluster translocation and localized actin polymerization.
- Integrin clusters serve as critical hubs for mechanotransduction and downstream signaling.
- Further research can explore synergistic interactions with activated integrin receptors.
Related Concept Videos
01:15Activation of Integrins
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
01:10Integrins
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
01:24Overview of Cell-Matrix Interactions
The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
01:26Tension Response at Adherens Junctions
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin homology) domains...
α-Catenin as a Mechanosensory Protein
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01:03Anchoring Junctions
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...