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09:14
Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
Model of integrin-mediated cell adhesion strengthening
Nathan D Gallant1, Andrés J García
1Woodruff School of Mechanical Engineering, 315 Ferst Drive, 2314, Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0363, USA.
Journal of Biomechanics
|July 11, 2006
Summary
This study models cell adhesion, showing how integrin bonds and focal adhesions strengthen cell connections to the extracellular matrix. Focal adhesion assembly significantly boosts adhesion strength beyond simple integrin clustering.
Area of Science:
- Biophysics
- Cell Biology
- Biomaterials Science
Background:
- Cell adhesion is crucial for tissue integrity and cellular functions.
- Integrins mediate cell adhesion by binding to extracellular matrix (ECM) components.
- Focal adhesions are dynamic structures formed during cell adhesion, involving integrins and the cytoskeleton.
Purpose of the Study:
- To develop a force balance model for cell adhesion to ECM.
- To analyze the impact of integrin bond properties and focal adhesion assembly on adhesion strength.
- To validate model predictions against experimental data.
Main Methods:
- A macroscopic-to-microscopic force balance model was developed.
- The model incorporated experimentally measured parameters like integrin bond force, number, and distribution.
- Focal adhesion assembly was included as a key factor in adhesion enhancement.
Main Results:
- Integrin bond force, number, and distribution significantly influenced overall adhesive force.
- Focal adhesion assembly increased adhesion strength by approximately 30% compared to integrin clustering alone.
- Model predictions showed excellent agreement with experimental results.
Conclusions:
- The developed model provides a quantitative framework for understanding cell adhesion mechanics.
- It highlights the distinct contributions of integrin binding and focal adhesion formation to adhesion strength.
- This model can be used to systematically analyze adhesive parameters and their effects on cell-matrix interactions.
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...
01:10Integrins
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,...
01:15Activation 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.
01:24Overview 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...
01:13Cell-matrix's Response to Mechanical Forces
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
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:...