Cell Biology: ECM Components and Transport Mechanisms
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Extracellular Matrix and Cell Adhesion
Key Components of the ECM
- Glycosaminoglycans (GAGs) are highly negatively charged polysaccharides that attract counterions and water, forming hydrated gels that resist compression and permit diffusion.
- Proteoglycans contain GAG chains attached to core proteins and contribute to this hydrated ECM.
- Multiadhesive proteins, such as fibronectin and laminin, bind multiple partners, including ECM components and cell-surface receptors.
- Integrins bind these adhesive proteins and connect the ECM to the cytoskeleton, allowing for adhesion, migration, force transmission, and bidirectional signaling.
The Process of Leukocyte Extravasation
- Leukocyte extravasation occurs through a sequence of rolling, activation, firm adhesion, and transmigration.
- First, endothelial E-selectins and P-selectins form weak interactions with leukocytes, causing the leukocytes to roll along the vessel wall.
- During activation, endothelial-presented chemokines bind GPCRs on the leukocyte and initiate inside-out signaling through talin and kindlin.
- Activated integrins then bind strongly to endothelial adhesion molecules, such as ICAM, producing firm adhesion and arrest.
- Finally, the leukocyte crosses the endothelial barrier and migrates into the inflamed tissue. Integrin engagement also initiates outside-in signaling through proteins such as FAK, promoting cytoskeletal rearrangement and migration.
Comparison of Membrane Transport Mechanisms
| Mechanism | Protein? | Direction | Energy | Saturable? | Example |
|---|---|---|---|---|---|
| Passive diffusion | No | Down gradient | Thermal motion; gradient | No | O2, CO2 |
| Facilitated diffusion | Yes | Down electrochemical gradient | Gradient | Yes for carriers | GLUT1; ion channels |
| Primary active transport | Pump | Against gradient | Direct ATP or another primary source | Yes | Na+/K+ ATPase |
| Secondary active transport | Cotransporter | One downhill drives one uphill | Stored ion gradient; indirect ATP dependence | Yes | SGLT2 |
Classification of ATP-Powered Pumps
| Class | Defining Mechanism | Typical Direction/Job | Examples |
|---|---|---|---|
| P-class | Pump becomes phosphorylated | ATP directly drives ion transport | Na+/K+ ATPase; H+/K+ ATPase; Ca2+ pumps |
| V-class | Rotary H+ pump; no phosphoenzyme intermediate | ATP → H+ gradient; acidification | Lysosome; endosome; synaptic vesicle |
| ABC | ATP-binding cassette domains | ATP-driven movement of diverse substrates | MDR drug efflux; lipid/cholesterol transport |
| F-class | Reversible rotary ATP synthase | Usually H+ gradient → ATP | Mitochondrial/bacterial ATP synthase |