How collagen interacts with cells?
Collagen is highly biologically active, interacting with cellular receptors, such as integrins, matrix metalloproteinases (MMPs) during degradation, and other ECM components. These collagen interactions are critical for biological function, however in other cases, improper interactions with collagen may be detrimental.
How does the ECM communicate with the cell?
Cells can communicate mechanically by responding either to mechanical deformations generated by their neighbors or to a change in the mechanical properties of the ECM induced by a neighboring cell.
Which integrin binds to collagen?
Integrin α1β1
Integrin α1β1 binds to collagen via the MIDAS motif in the α subunit I domain. It preferentially binds collagens IV, VI and type XIII collagen, but also fibril-forming collagens.
Where is collagen transported?
Moreover, collagen molecules self-assemble into structures of increasing size with each successive stage in the secretory pathway. The transported cargo increases from ∼0.5 MDa in the endoplasmic reticulum (ER) to several teradaltons (TDa) at the plasma membrane where the molecules are organized into fibrils.
What does collagen attach to?
Collagen is one of two fibrous connective tissue proteins. It is the principal component of tendons, which attach muscle to bone, and the connective tissue within and around muscles. Collagen frequently is described as a “coiled coil,” because three helical polypeptide chains are entwined.
What naturally occurring molecules interact with collagen?
Collagens are found in the extracellular matrix where they are assembled into fibrils and other supramolecular structures. Normal growth and development are dependent on the proper assembly of collagens. Collagens interact with three types of receptors: integrins, discoidins, and glycoprotein VI.
How does the extracellular matrix control the growth of cells?
The extracellular matrix helps cells to bind together and regulates a number of cellular functions, such as adhesion, migration, proliferation, and differentiation. It is formed by macromolecules, locally secreted by resident cells. This structure enables the cell to adhere to the substratum.
What type of adhesive ECM molecule would help hold the collagen together?
Cell adhesion proteins Fibronectins are glycoproteins that connect cells with collagen fibers in the ECM, allowing cells to move through the ECM. Fibronectins bind collagen and cell-surface integrins, causing a reorganization of the cell’s cytoskeleton to facilitate cell movement.
How is collagen stabilized?
A collagen triple helix has 3.3 residues per turn. Each of the three chains is stabilized by the steric repulsion due to the pyrrolidine rings of proline and hydroxyproline residues. The hydrogen bond acceptors are the CO groups of residues on the other chains.
How is collagen transported across the cell membrane?
Collagen connects to integrin proteins in the plasma membrane via fibronectin. Proteins in the extracellular matrix, like the fibronectin molecules shown in green in the diagram above, can act as bridges between integrins and other extracellular matrix proteins such as collagen.
What holds collagen together?
Hydrogen bonding helps collagen to form its ‘tertiary’ structure. The hydrogen bonds are very strong and keep the connective tissues in the body together.
How do cancer cells communicate with collagen?
Cancer cells further communicate with collagen via signaling pathways during the processes of cellular metabolism, proliferation, differentiation, and apoptosis. Transforming growth factor-β (TGF-β)/Smad signaling is a typical component of serine/threonine kinase signal transduction.
Can collagen biosynthesis regulate cancer cells?
Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways.
What is collagen and how does it affect cancer fibrosis?
Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis.
What is the pathophysiology of extensive collagen deposition?
In addition, extensive collagen deposition is the main pathological characteristic of some cancers, for which sufficient therapeutic applications are lacking, resulting in the poor survival outcomes of patients [ 7 ].