Related Experiment Video
Updated: May 20, 2026
09:14
Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
NELL-1 promotes cell adhesion and differentiation via Integrinβ1.
Jia Shen1, Aaron W James, Jonguk Chung
1Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Journal of Cellular Biochemistry
|July 19, 2012
Summary
Nel-like molecule-1 (NELL-1) binds to Integrinβ1, enhancing cell adherence and osteogenic differentiation. This discovery reveals NELL-1’s cell surface receptor and its role in bone formation.
Area of Science:
- Biochemistry
- Cell Biology
- Biomaterials Science
Background:
- Nel-like molecule-1 (NELL-1) is a secreted protein implicated in bone and cartilage development.
- NELL-1 has been identified in craniosynostosis patients and shown to promote osteogenesis and suppress adipogenesis.
- The specific cell surface receptors mediating NELL-1's functions remained unidentified.
Purpose of the Study:
- To identify the cell surface receptor(s) for NELL-1.
- To investigate NELL-1's role in cell adherence and focal adhesion.
- To determine if NELL-1 can enhance osteogenic differentiation on biomaterial scaffolds.
Main Methods:
- Tested NELL-1's effect on cell adherence in various cell lines (ST2, C3H10T1/2, M2-10B4, ATDC5, MC3T3).
- Utilized siRNA to assess the role of Integrinβ1 in NELL-1 binding and cell attachment.
- Coated culture dishes and PLGA scaffolds with NELL-1 to evaluate effects on cell attachment and osteogenic differentiation.
Main Results:
- NELL-1 significantly increased cell adherence across multiple cell lines.
- NELL-1 was found to bind to extracellular Integrinβ1, inducing focal adhesion.
- Integrinβ1 expression was essential for NELL-1's cell surface binding and enhanced attachment.
- Pre-coating with NELL-1 promoted cell attachment and osteogenic differentiation on culture dishes and PLGA scaffolds.
Conclusions:
- Identified Integrinβ1 as the cell surface receptor for NELL-1.
- Demonstrated NELL-1's novel functions in promoting cell adherence and focal adhesion.
- Established NELL-1's potential as a therapeutic agent to enhance osteogenic differentiation on biomaterials.
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...
01:03Anchoring 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:...
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...