Assembly Of Collagen Molecules Research Articles

Impacts of fullerene derivatives on regulating the structure and assembly of collagen molecules

During cancer development, the fibrous layers surrounding the tumor surface get thin and stiff which facilitates the tumor metastasis. After the treatment of metallofullerene derivatives Gd@C82(OH)22, the fibrous layers become thicker and softer, the metastasis of tumor is then largely suppressed. The effect of Gd@C82(OH)22 was found to be related to their direct interaction with collagen and the resulting impact on the structure of collagen fibrils, the major component of extracellular matrices. In this work we study the interaction of Gd@C82(OH)22 with collagen by molecular dynamics simulations. We find that Gd@C82(OH)22 can enhance the rigidity of the native structure of collagen molecules and promote the formation of an oligomer or a microfibril. The interaction with Gd@C82(OH)22 may regulate further the assembly of collagen fibrils and change the biophysical properties of collagen. The control run with fullerene derivatives C60(OH)24 also indicates that C60(OH)24 can influence the structure and assembly of collagen molecules as well, but to a lesser degree. Both fullerene derivatives can form hydrogen bonds with multiple collagen molecules acting as a "fullerenol-mediated bridge" that enhance the interaction within or among collagen molecules. Compared to C60(OH)24, the interaction of Gd@C82(OH)22 with collagen is stronger, resulting in particular biomedical effects for regulating the biophysical properties of collagen fibrils.

In Situ D-periodic Molecular Structure of Type II Collagen

Collagens are essential components of extracellular matrices in multicellular animals. Fibrillar type II collagen is the most prominent component of articular cartilage and other cartilage-like tissues such as notochord. Its in situ macromolecular and packing structures have not been fully characterized, but an understanding of these attributes may help reveal mechanisms of tissue assembly and degradation (as in osteo- and rheumatoid arthritis). In some tissues such as lamprey notochord, the collagen fibrillar organization is naturally crystalline and may be studied by x-ray diffraction. We used diffraction data from native and derivative notochord tissue samples to solve the axial, D-periodic structure of type II collagen via multiple isomorphous replacement. The electron density maps and heavy atom data revealed the conformation of the nonhelical telopeptides and the overall D-periodic structure of collagen type II in native tissues, data that were further supported by structure prediction and transmission electron microscopy. These results help to explain the observed differences in collagen type I and type II fibrillar architecture and indicate the collagen type II cross-link organization, which is crucial for fibrillogenesis. Transmission electron microscopy data show the close relationship between lamprey and mammalian collagen fibrils, even though the respective larger scale tissue architecture differs.

Strain Differences and the Role for HSP47 and HSP70 in Adjuvant Arthritis in Rats

Because of high sequence homology between microbial and endogenous heat shock proteins (HSP), immunological cross-reactivity to microbial HSP has been suggested as a possible cause of the development of autoimmune diseases, such as rheumatoid arthritis. The present study aimed to determine a potential role of HSP47, a molecular chaperone involved in the synthesis and assembly of collagen molecules, and microbial HSP71 (mHSP71) in adjuvant arthritis (AA) in two rat strains: Dark Agouti (DA), susceptible to AA induction and Albino Oxford (AO), which is resistant to AA induction. Immunization with complete Freund's adjuvant (CFA) induced an increased expression of HSP47 in joints of DA rats, which exhibited severe clinical signs of AA at the time of disease peak, while this protein was not detectable in joints of AO rats. In contrast, no strain differences in HSP72 (rat analogue of mHSP71) expressions in joints were observed. The increased levels of anti-HSP47 antibodies were detected in sera of DA rats during the AA peak, while the immunization with CFA increased levels of anti-mHSP71 antibodies in sera of AO rats. HSP47 and mHSP71 reduced proliferation of draining inguinal lymph node cells (LNC) in resistant AO rat strain, leading to a hypothesis that both HSP participated in AA control. Finally, mHSP71 potentiated the apoptotic response of LNC in susceptible DA rat strain. In conclusion, our findings indicate involvement of HSP47 in the development of AA in the rat, and point out to the regulatory role for both HSP47 and mHSP71.

Collagen fibril and matrix assembly during morphogenesis

The morphogenesis of the extracellular matrix requires the synthesis, assembly and deposition of collagen in a tissue specific manner. Collagen synthesis and molecular assembly occur within a series of well defined cytoplasmic compartments, while the assembly and deposition of collagen fibrils, fibril bundles and collagen macroaggregates occurs within a series of extracellular compartments. In the studies described here we focus our attention on the assembly of collagen molecules into fibrils, bundles and tissue specific macroaggregates.The fibroblast has a complex topography which serves to partition the extracellular space into distinct domains where the hierarchical stages in matrix assembly occur. The first recognizable extracytoplasmic domain is a narrow channel which originates deep within the cytoplasm and is open to the extracellular space. These narrow spaces contain single or sometimes 2-3 collagen fibrils and are intimately associated with secretory vacuoles. These channels fuse with each other and with the cell surface giving rise to the second level of compartmentalization and matrix hierarchy where fibrils coalesce to form bundles.

Extracellular matrix morphogenesis: HVEM analysis

Matrix morphogenesis requires the synthesis, assembly and deposition of collagen molecules in a tissue specific manner. Collagen fibrillogenesis is a multistep process involving both intracellular and extracellular assembly reactions. Collagen synthesis, molecular assembly and formation of supramolecular aggregates occurs within a series of well defined cytoplasmic compartments while the assembly and deposition of the newly synthesized collagen fibrils, fibril bundles and tissue specific collagen macroaggregates occurs within a series of extracellular compartments defined by the fibroblast.In the studies described here we will focus our attention on the cellular influences involved in the assembly of collagen molecules into fibrils, fibril bundles and tissue specific macroaggregates. The chick tendon and corneal fibroblasts partition the extracellular space during morphogenesis, forming at least three compartments. These extracytoplasmic compartments have been described using high voltage electron microscopy of thick sections and serial thick sections as well as by conventional transmission electron microscopy.