L13: Extra reading Flashcards
fibronectin
Parisi et al. (2019)
Fibronectin (FBN) is an extracellular matrix (ECM) component that, through binding integrin receptors of the cell surface, acts as a key player of the communication between the intra and the extracellular environment, thus controlling cell behavior. Furthermore, in regenerative dentistry the role of FBN in promoting the attachment of cells to root surface has been shown, as well as FBN probable pivotal role in bone and periodontal regeneration is of considerable interest [5]. Therefore, the modulation of integrin-FBN interaction may offer a promising approach to tailor tissue regenerative responses, i.e. bone and periodontal regeneration [6].
fibronectin in cell migration
The abundance of FBN in the clot is closely related to fibroblasts recruitment during wound healing. As such, FBN introduction on biomaterials may allow the creation of dynamic pathway for cells to move along the scaffold [26]. This implies FBN might act as a migratory signal or scaffold for these cells.
Accordingly, Nuttelman et al. (2001) observed that NIH3T3 fibroblasts migrated faster on poly(vinyl alcohol) hydrogels modified with FBN, if compared to tissue culture plate and to control hydrogels [26]. Similarly, by means of aptamers selected to recognize and bind FBN, we were so far able to improve the migratory capacity of osteoblasts into a hyaluronic acid based matrix [27].
i.e: enhanced cell migration
the ecm in cell migration
Pally and Naba (2024)
Cells secrete and deposit their ECM and actively organize it through cell surface receptors to facilitate their migration (Figure 2(a)). Fibronectin is one of the most abundant and well-studied fibrillar ECM proteins, and the mechanisms leading to its assembly mediated by integrin receptors is now well characterized in vitro [14]. Interestingly, recent experiments on the developing chicken embryo and associated computational modeling have demonstrated a novel mode of fibronectin organization mediated by migrating neural crest cells (NCCs). During NCC migration into the cranial region, leader cells remodel the unorganized and punctate fibronectin into a linear and filamentous form. Newly organized fibronectin then not only acts as a directional cue for efficient migration of follower cells [15] but also contributes to the assembly of other ECM proteins affecting overall ECM architecture. Similarly, during craniofacial skeleton development in mice, the interaction between skeletal progenitor cells and the collagen-rich ECM regulates proliferation, migration, and differentiation [16]. Loss of expression or mutations in discoidin domain receptor 2 (DDR2), a known collagen receptor, causes craniofacial malformations [17].
ecm in parkinsons
Rike and stern (2023)
Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson’s Disease: A Systematic Review
According to proteomic studies, proteins such as collagens, fibronectin, annexins, and tenascins were recognized to be differentially expressed in Parkinson’s disease. Transcriptomic studies displayed dysregulated pathways including ECM-receptor interaction, focal adhesion, and cell adhesion molecules in Parkinson’s disease. A limited number of relevant studies were accessed from our search, indicating that much work remains to be carried out to better understand the roles of the ECM in neurodegeneration and Parkinson’s disease. However, we believe that our review will elicit focused primary studies and thus support the ongoing efforts of the discovery and development of diagnostic biomarkers as well as therapeutic agents for Parkinson’s disease.
from the stem cell lecture
- While ECM components remain relativley consistent across tissues and developmental stages, they can have considerable anatomical and molecular variation in their expression. For instance, laminins and integrins show heterogeinity in different areas of the skin BM, showing distinct adhesive properties that may be important for maintaining epidermal stem cells.
- “The extracellular matrix plays a crucial role not only in providing structural support but also in regulating cell behavior. In the context of the stem cell niche, the ECM is essential for anchoring stem cells in close proximity to self-renewal and survival signals. This spatial positioning ensures that stem cells receive the necessary biochemical and mechanical cues to maintain their undifferentiated state and proliferative capacity.”
Non-cellular niches: Composed of extracellular matrix (ECM), such as in muscles where satellite cells remain in the basal lamina to maintain an undifferentiated state.
“Cell adhesion plays a critical role in stem cell-niche interactions. For instance, in the bone marrow, cadherin-mediated adhesion facilitates hematopoietic stem cell (HSC) association with osteoblasts via N-cadherin. Additionally, high levels of β1 integrin are characteristic of HSCs, mediating interactions with the extracellular matrix. Other adhesion-related receptors such as c-kit, CXCR4, and membrane-bound steel factor (SLF) contribute to HSC retention within the niche, further illustrating how adhesion molecules govern both structural and signaling roles.”
GAGs
Glycosaminoglycans ( GAGs ) are unbranched polysaccharide chains composed of repeating disaccharide units. One of the two sugars in the repeating disaccharide is always an amino sugar ( N -acetylglucosamine or N -acetylgalactosamine), which in most cases is sulfated. The second sugar is usually a uronic acid (glucuronic or iduronic). Because there are sulfate or carboxyl groups on most of their sugars, GAGs are highly negatively charged ( Figure 19– 32 ). Indeed, they are the most anionic molecules produced by animal cells. Four main groups of GAGs are distinguished by their sugars, the type of linkage between the sugars, and the number and location of sulfate groups: (1) hyaluronan , (2) chondroitin sulfate and dermatan sulfate , (3) heparan sulfate , and (4) keratan sulfate . Polysaccharide chains are too stiff to fold into compact globular structures, and they are strongly hydrophilic. Thus, GAGs tend to adopt highly extended conformations that occupy a huge volume relative to their mass ( Figure 19– 33 ), and they form hydrated gels even at very low concentrations. The weight of GAGs in connective tissue is usually less than 10% of the weight of proteins, but GAG chains fill most of the extracellular space. Their high density of negative charges attracts a cloud of cations, especially Na + , that are osmotically active, causing large amounts of water to be sucked into the matrix. This creates a swelling pressure, or turgor, that enables the matrix to withstand compressive forces (in contrast to collagen fibrils, which resist stretching forces). The cartilage matrix that lines the knee joint, for example, can support pressures of hundreds of atmospheres in this way. Defects in the production of GAGs can affect many different body systems. In one rare human genetic disease, for example, there is a severe deficiency in the synthesis of dermatan sulfate disaccharide. The affected individuals have a short stature, a prematurely aged appearance, and generalized defects in their skin, joints, muscles, and bones. type IV collagen fibrillar collagen glycoproteins laminin nidogen fibronectin 100 nm Figure 19– 31 The comparative shapes and sizes of some of the major extracellular matrix macromolecules. Protein is shown in green , and glycosaminoglycan (GAG) in red. MBoC6 m19.41/19.32
Bruce, Alberts, et al. Molecular Biology of the Cell, Taylor & Francis Group, 2014. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/kcl/detail.action?docID=5320520.
Created from kcl on 2025-04-27 16:43:33.
hyloronan
Hyaluronan is thought to have a role in resisting compressive forces in tissues and joints. It is also important as a space filler during embryonic development, where it can be used to force a change in the shape of a structure, as a small quantity expands with water to occupy a large volume. Hyaluronan synthesized locally from the basal side of an epithelium can deform the epithelium by creating a cellfree space beneath it, into which cells subsequently migrate. In the developing heart, for example, hyaluronan synthesis helps in this way to drive formation of the valves and septa that separate the heart’s chambers. Similar processes occur in several other organs. When cell migration ends, the excess hyaluronan is generally degraded by the enzyme hyaluronidase . Hyaluronan is also produced in large quantities during wound healing, and it is an important constituent of joint fluid, in which it serves as a lubricant. globular protein (MW 50,000) glycogen (MW ~400,000) spectrin (MW 460,000) collagen (MW 290,000) hyaluronan (MW 8 x 10 6 ) 300 nm Figure 19– 33 The relative dimensions and volumes occupied by various macromolecules. Several proteins, a glycogen granule, and a single hydrated
Bruce, Alberts, et al. Molecular Biology of the Cell, Taylor & Francis Group, 2014. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/kcl/detail.action?docID=5320520.
Created from kcl on 2025-04-27 16:44:46.
proteoglycans
Except for hyaluronan, all GAGs are covalently attached to protein as proteoglycans , which are produced by most animal cells. Membrane-bound ribosomes make the polypeptide chain, or core protein , of a proteoglycan, which is then threaded into the lumen of the endoplasmic reticulum. The polysaccharide chains are mainly assembled on this core protein in the Golgi apparatus before delivery to the exterior of the cell by exocytosis. First, a special linkage tetrasaccharide is attached to a serine side chain on the core protein to serve as a primer for polysaccharide growth; then, one sugar at a time is added by specific glycosyl transferases ( Figure 19– 35 ). While still in the Golgi apparatus, many of the polymerized sugars are covalently modified by a sequential and coordinated series of reactions. Epimerizations alter the configuration of the substituents around individual carbon atoms in the sugar molecule; sulfations increase the negative charge. Proteoglycans are clearly distinguished from other glycoproteins by the nature, quantity, and arrangement of their sugar side chains. By definition, at least one of the sugar side chains of a proteoglycan must be a GAG. Whereas glycoproteins generally contain relatively short, branched oligosaccharide chains that contribute only a small fraction of their weight, proteoglycans can contain as much as MBoC6 m19.56/19.34
Bruce, Alberts, et al. Molecular Biology of the Cell, Taylor & Francis Group, 2014. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/kcl/detail.action?docID=5320520.
Created from kcl on 2025-04-27 16:45:24.
collagen
The collagens are a family of fibrous proteins found in all multicellular animals. MBoC6 m19.60/19.38 They are secreted in large quantities by connective-tissue cells, and in smaller quantities by many other cell types. As a major component of skin and bone, collagens are the most abundant proteins in mammals, where they constitute 25% of the total protein mass. The primary feature of a typical collagen molecule is its long, stiff, triple-stranded helical structure, in which three collagen polypeptide chains, called α chains , are wound around one another in a ropelike superhelix ( Figure 19– 39 ). FThe human genome contains 42 distinct genes coding for different collagen α chains. Different combinations of these genes are expressed in different tissues. Although in principle thousands of types of triple-stranded collagen molecules could be assembled from various combinations of the 42 α chains, only a limited number of triple-helical combinations are possible, and roughly 40 types of collagen molecules have been found. Type I is by far the most common, being the principal collagen of skin and bone. It belongs to the class of fibrillar collagens , or fibril-forming collagens: after being secreted into the extracellular space, they assemble into higher-order polymers called collagen fibrils , which are thin structures (10– 300 nm in diameter) many hundreds of micrometers long in mature tissues, where they are clearly visible in electron micrographs ( Figure 19– 40 ; see also Figure 19– 38). Collagen fibrils often aggregate into larger, cablelike bundles, several micrometers in diameter, that are visible in the light microscope as collagen fibers . Collagen types IX and XII are called fibril-associated collagens because they decorate the surface of collagen fibrils. They are thought to link these fibrils to one another and to other components in the extracellular matrix. Type IV is a network-forming collagen , forming a major part of basal laminae, while type VII molecules form dimers that assemble into specialized structures called anchoring fibrils. Anchoring fibrils help attach the basal lamina of multilayered epithelia to the underlying connective tissue and therefore are especially abundant in the skin. There are also a number of “collagen-like” proteins containing short collagen-like segments. These include collagen type XVII, which has a transmembrane domain and is found in hemidesmosomes, and type XVIII, the core protein of a proteoglycan in basal laminae. Many proteins appear to have evolved by repeated duplications of an original DNA sequence, giving rise to a repetitive pattern of amino acids. The genes that encode the α chains of most of the fibrillar collagens provide a good example: they are very large (up to 44 kilobases in length) and contain about 50 exons. Most of glycine (A) x y y y y y y y x y x y x x x x x x x y (B)
Bruce, Alberts, et al. Molecular Biology of the Cell, Taylor & Francis Group, 2014. ProQuest Ebook Central, http://ebookcentral.proquest.com/lib/kcl/detail.action?docID=5320520.
Created from kcl on 2025-04-27 16:46:36.
