Related Experiment Video
Updated: May 18, 2026
09:14
Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
A spatial model for integrin clustering as a result of feedback between integrin activation and integrin binding
Erik S Welf1, Ulhas P Naik, Babatunde A Ogunnaike
1Department of Chemical Engineering, University of Delaware, Newark, Delaware, USA.
Biophysical Journal
|September 22, 2012
Summary
Cellular integrin clusters form through a biochemical feedback mechanism involving active integrins and talin, independent of actin stress fibers. This model explains how localized activation drives integrin clustering for cell migration.
Area of Science:
- Cell Biology
- Biophysics
- Molecular Cell Biology
Background:
- Integrins are transmembrane receptors crucial for cell adhesion and migration by binding extracellular matrix (ECM) proteins.
- Integrin clusters at cell-ECM contacts form adhesion complexes that mediate force transfer, but their formation regulation is poorly understood.
- Integrin cluster formation requires active integrins, phosphoinositol-4,5-bisphosphate (PIP2), talin, and immobile ECM ligands, but is independent of actin stress fibers.
Purpose of the Study:
- To propose and model a mechanism for the initial formation of integrin clusters.
- To investigate the role of biochemical feedback in regulating integrin cluster assembly.
- To understand how localized integrin activation contributes to spatial organization.
Main Methods:
- Utilized a diffusion-reaction framework to model the biochemical reactions involved in integrin clustering.
- Developed a minimal model based on known requirements for integrin cluster formation.
- Simulated the effects of localized activation and positive feedback on integrin cluster dynamics.
Main Results:
- Demonstrated that a local source of active integrins, facilitated by protein complexes, can lead to spatial organization into clusters.
- Showed that positive feedback between integrin binding and activation can amplify small increases in active talin or integrin concentrations.
- Identified that integrin cluster formation is dependent on the balance between production and diffusion of integrin-activating species.
Conclusions:
- The proposed model provides a mechanism for integrin cluster formation driven by localized integrin activation and biochemical feedback.
- Positive feedback loops involving talin and active integrins are critical for initiating and stabilizing integrin clusters.
- The relative rates of production and diffusion of activating species influence the properties of the resulting integrin clusters, impacting cell migration.
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...
01:31Immunoglobulin-like Cell Adhesion Molecules
Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
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:...