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Updated: May 23, 2026
09:14
Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion
Jacob Rullo1, Henry Becker, Sharon J Hyduk
1Toronto General Research Institute, University Health Network, Toronto, M5G 2C4 Ontario, Canada. jacob.rullo@utoronto.ca
The Journal of Cell Biology
|April 5, 2012
Summary
Leukocytes resist blood flow forces by rapidly polymerizing actin at adhesion sites, forming structures that stabilize their attachment to inflamed endothelium. This process involves specific signaling pathways, preventing cell detachment.
Area of Science:
- Immunology
- Cell Biology
- Biophysics
Background:
- Leukocytes adhere to inflamed endothelium via integrins, experiencing forces from blood flow.
- The mechanisms by which leukocytes resist these detachment forces are not fully understood.
Purpose of the Study:
- To investigate how leukocytes respond to mechanical forces and maintain adhesion.
- To identify the signaling pathways and structural changes involved in leukocyte adhesion stabilization.
Main Methods:
- Live-cell imaging of Lifeact-transfected U937 cells under flow.
- Scanning electron microscopy to visualize adhesion structures.
- Inhibition of actin polymerization and key signaling molecules (Rap1, PI3Kγ, Rac).
Main Results:
- Mechanical force triggers actin polymerization at upstream integrin adhesion sites.
- This actin polymerization forms structures that anchor monocyte adhesion.
- Inhibiting actin polymerization leads to cell deformation, displacement, and detachment.
- Key signaling molecules (Rap1, PI3Kγ, Rac) are crucial for actin polymerization and adhesion stabilization.
Conclusions:
- Leukocytes utilize rapid signaling and structural adaptations to stabilize adhesion.
- Actin polymerization is essential for resisting detachment forces during inflammation.
- Specific signaling pathways mediate force-induced adhesion strengthening in leukocytes.
Related Concept Videos
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...
01:13Actin Polymerization and Cell Motility
Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate.
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.
01:10Integrins
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,...
01:42Actin Polymerization
Actin polymerization occurs through the head-to-tail association of binding sites on monomeric actin or G-actin to form filamentous or F-actin. The polymerization can be divided into three phases ̶ nucleation, elongation, and steady-state phase.
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
The nucleation phase involves forming a stable nucleus consisting of three actin monomers to form a new actin filament. Actin-binding proteins such as formins and Arp2/3 complex help filament growth post-nucleation. The Formins form straight actin...
01:39Mechanism of Filopodia Formation
Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...