Extracellular Matrix and Collagen Overview

The ECM is a network of extracellular materials that surrounds cells. It regulates cell shape, adhesion, migration, growth, and differentiation. It consists of proteins such as collagen and components like proteoglycans.

The ECM influences cellular behavior by regulating activities such as migration, growth, and differentiation through cell-surface receptors.

Cells lose their differentiated state, appear flattened, and their secretory activities decrease. Reintroducing ECM materials restores differentiation.

The ECM is most prominent in connective tissues such as cartilage, bones, tendons, and the corneal stroma. These tissues derive their properties (e.g., flexibility, hardness, tensile strength, transparency) from the ECM.

The basement membrane provides mechanical support, generates survival signals, facilitates cell migration, separates tissues, and acts as a barrier to cancer cells and macromolecules.

Collagen is the most abundant protein in the human body, constituting more than 25% of total protein.

Collagen molecules are trimers of three polypeptide chains that form a triple helix. Some assemble into fibrils and then into fibers.

This staggered arrangement provides strength and creates a characteristic banding pattern through covalent cross-links between lysine and hydroxylysine.

Collagen fibrils in connective tissues are organized in orthogonal layers, meaning they are parallel within a layer but perpendicular to adjacent layers. This structure provides strength and maintains transparency by reducing light scattering.

Type IV collagen trimers in basement membranes contain interspersed nonhelical segments, which give the membrane flexibility and a lattice-like structure. This allows for the deposition of extracellular matrix (ECM) materials.

GAGs are acidic polysaccharides with repeating disaccharide units. Their negative charges attract cations and water, forming hydrated gels that resist compression forces.

Proteoglycans can occupy a lot of space due to their hydrated gels, which are created by their ability to bind water. These gels provide resistance to compression and contribute to the mechanical strength of tissues like cartilage.

Laminin is a protein that supports cell migration, growth, and differentiation. It provides migration paths for specific cells, such as primordial germ cells during development.

Matrix metalloproteinases (MMPs) are enzymes responsible for the degradation of extracellular matrix (ECM) components. This process is crucial for tissue remodeling and other biological events.

Integrins are transmembrane proteins that attach cells to the extracellular matrix (ECM). They mediate bidirectional signaling (inside-out and outside-in), influencing adhesion, migration, and intracellular signaling cascades.

When cells from different developing organs are mixed, they self-sort into homogeneous clusters. This process is driven by cell adhesion and communication, and it leads to the differentiation of cells into the structures they would form in an intact embryo.

Ligands binding to receptors trigger various intracellular changes, like altering pH, Ca²⁺ levels, protein phosphorylation, and gene expression. These changes ultimately dictate cell behavior, including growth and differentiation.

Culturing mammary cells in the presence of extracellular glycoproteins like laminin promotes cell differentiation, organization into milk-producing structures, and restoration of milk protein production.

Gap junctions facilitate direct communication between cells, allowing the passage of ions and small molecules, ensuring coordinated cellular activity.

Connexons from neighboring cells align and link together to form intercellular channels, creating direct cytoplasmic connections between cells.

Plants lack cell adhesion molecules and have cell walls, preventing the formation of specialized junctions found in animal cells, where cells are in direct contact.

Plasmodesmata are cylindrical channels lined by the plasma membrane and containing a central desmotubule derived from the smooth ER.

Certain viruses encode movement proteins that enlarge plasmodesmata, allowing larger viral particles to pass through, facilitating cell-to-cell spread.

Pectin, a cell wall component, is commercially valuable for its gel-forming properties, used in products like jams and jellies.

Fractionation is the separation of cell components based on their properties, often using techniques like density-gradient centrifugation.

Vesicles from different parts of the Golgi complex have distinct lipid and protein compositions, reflecting their unique functions and destinations.

Proteins synthesized by free ribosomes remain in the cytosol or are directed to specific locations within the cell based on signal sequences.

A mutation preventing vesicle formation at the ER membrane leads to expanded ER cisternae, indicating an inability to package and transport proteins.

A mutation disrupting vesicle fusion results in an accumulation of unfused vesicles, indicating a failure in merging with target membranes.

The interconnectedness of RER and SER membranes can be demonstrated by observing the diffusion of fluorescently labeled lipids or proteins between these compartments.

The rough ER synthesizes proteins, while the smooth ER synthesizes lipids, detoxifies substances, and regulates calcium.

Secretory cells have a specific organelle arrangement: RER at the basal end for protein synthesis, Golgi complex in the center for processing and sorting, and secretory vesicles at the apical end for discharge.

A pathway that transports materials synthesized in the ER to the Golgi and then to various destinations within and outside the cell.

A pathway that moves materials from the cell surface into cytoplasmic compartments like lysosomes.

The Golgi apparatus modifies and packages lipids, carbohydrates, and certain glycoproteins.

The continuous, unregulated release of substances from the cell.

Proteins have specific sorting signals, either in their amino acid sequence or attached sugars, recognized by receptors that direct them to the right location.

Short sequences of amino acids or attached sugars on proteins that act as labels, recognized by receptors on the surface of vesicles to direct them to the correct destination.

A technique for studying protein transport using radioactive amino acids, where a brief 'pulse' of labeling is followed by a 'chase' with unlabeled amino acids.

A technique using green fluorescent protein (GFP) fused to the gene encoding a specific protein, allowing visualization of its dynamic movements in a living cell.

Asymmetry in cell membranes is established during synthesis in the ER and preserved throughout vesicle trafficking. Mechanisms like enzymatic modifications, selective inclusion during budding, and phospholipid-transfer proteins contribute to this.

Carbohydrate groups on glycoproteins serve various functions, including aiding proper protein folding, acting as binding sites for other molecules, and protecting proteins from degradation.

Yes, the sequence of sugars in secretory glycoproteins is predictable. The specific location and activity of glycosyltransferases in the Golgi complex determine the order of sugar addition.

GT (glycosyltransferase) binds to exposed hydrophobic residues on misfolded proteins, indicating a lack of proper folding. This binding triggers glucose addition to the protein.

The accumulation of misfolded proteins in the ER triggers the unfolded protein response (UPR), which increases chaperone production and reduces protein synthesis.

Sensors in the ER monitor unfolded proteins by either directly binding to them or by sensing stress within the ER membrane.

The cisternal maturation model proposes that Golgi cisternae are dynamic structures that move from the cis face to the trans face, undergoing changes during their journey.

Retrograde transport is the movement of vesicles from the trans to the cis end of the Golgi complex, carrying proteins and other molecules back to earlier compartments.