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Biomedical subjects

D F Mosher

Publications and source records attributed to D F Mosher.

At least 73 records · Page 4Linked to original sources
PubMed1994

Baculovirus-mediated expression of the epidermal growth factor-like modules of human factor IX fused to the factor XIIIa transamidation site in fibronectin. Evidence for a direct interaction between the NH2-terminal epidermal growth factor-like module of factor IXa beta and factor X.

Factor IX is a vitamin K-dependent procoagulant zymogen of a serine protease. In the presence of Ca2+ the active form of factor IX (factor IXa beta) forms a complex with factor VIIIa on suitable phospholipid surfaces such as aggregated platelets. This macromolecular complex rapidly activates factor X. We have previously provided data that suggest an interaction between the NH2-terminal epidermal growth factor (EGF)-like module of factor IXa beta and the substrate factor X. In an alternative approach to study this protein-protein interaction, we have expressed three recombinant baculovirus constructs encoding the EGF-like modules of human factor IX and a truncated form of fibronectin in a system based on the infection of insect cells (Spodoptera frugiperda 21). This strategy allows a simple one-step purification of the recombinant proteins on a gelatin-Sepharose column, followed by removal of the gelatin-binding part derived from fibronectin by proteolytic cleavage. The fusion proteins were isolated at yields of 20-50 micrograms/ml culture medium. The recombinant EGF-like modules contained 0.2-0.4 mol of erythro-beta-hydroxyaspartic acid/mol of protein, i.e. similar to the amount found in factor IX from human plasma, and appeared to be glycosylated at Ser-53. The NH2-terminal EGF-like module, which contained a transamidation acceptor site derived from fibronectin, was cross-linked by factor XIIIa in solution to intact and Gla-domainless factor X. There was no evidence of cross-linking to activated factor X or to factor X fragments containing only the gamma-carboxyglutamic acid module and the two EGF-like modules. The cross-linking results suggest a specific interaction between the NH2-terminal EGF-like module of factor IXa beta and the heavy chain of unactivated factor X. This interaction, albeit weak as judged by competition experiments, may be important for the targeting of factor X to the factor IXa beta-factor VIIIa complex on biological membranes and for the subsequent dissociation of factor Xa from the complex after activation.

Amino Acid Sequence↗
PubMed1994

Synthesis, surface, and cell-adhesion properties of polyurethanes containing covalently grafted RGD-peptides.

In an attempt to improve endothelial cell adhesion and growth on a polyurethane copolymer, cell adhesive RGD-containing peptides were grafted to the polymer backbone. Two peptide grafting reaction schemes, including one-step and two-step approaches, were developed. FTIR and amino acid analysis confirmed that coupling of the peptide to the polyurethane backbone was achieved by both the one-step and two-step methods. However, the two-step approach showed a higher peptide coupling efficiency and resulted in better control of the orientation of the grafted peptide. The two-step reaction scheme was used to prepare Gly-Arg-Gly-Asp-Ser-Tyr (GRGDSY), Gly-Arg-Gly-Asp-Val-Tyr (GRGDVY), and Gly-Arg-Gly-Glu-Ser-Tyr (GRGESY) peptide-grafted polyurethanes with two different peptide densities (100 and 250 mumol/g polymer). Dynamic contact angle measurements indicated that the surfaces of the peptide-grafted polyurethanes were more hydrophilic than the starting and carboxylated versions of the precursor polyurethane. In addition, the surface hydrophilicity of the peptide-grafted polymers increased with increasing bulk peptide density. Electron spectroscopy for chemical analysis suggested that the grafted peptide was present at the polymer-air interface, in vacuo, for the peptide-grafted polyurethanes. The surface peptide density appeared to correlate with the incorporated peptide density in the bulk. In vitro endothelial cell adhesion experiments showed that, without the presence of serum in culture medium, the GRGDSY- and GRGDVY-grafted polyurethanes dramatically enhanced cell attachment and spreading compared with the starting, carboxylated, and GRGESY-grafted polymers. Increasing the peptide density from 100 to 250 mumol/g polymer for the GRGDSY- and GRGDVY-grafted polyurethanes resulted in an increase in cell attachment. With approximately the same peptide density (100 or 250 mumol/g polymer), the GRGDVY-grafted polymers supported more adherent cells than did the GRGDSY-grafted polymers. Similar trends were observed in the in vitro endothelial cell growth studies using culture medium containing serum and endothelial cell growth supplement. The GRGDSY- and GRGDVY-grafted polyurethanes promoted more cell growth than did the starting polyurethane. However, the presence of adhesive serum proteins and growth factor diminished the differences between the cell-adhesive peptide grafted polymers and the GRGESY-grafted polymers.

Amino Acid Sequence↗
PubMed1994

Modulation of cell surface fibronectin assembly sites by lysophosphatidic acid.

Lysophosphatidic acid is a product of activated platelets and has diverse actions on cells. We have characterized the effect of lysophosphatidic acid on cell-mediated binding and assembly of fibronectin, an extracellular matrix protein. Serum made from whole blood, but neither platelet-poor plasma nor serum made from platelet-poor plasma, caused enhanced binding of fibronectin to cultured fibroblastic cells. The ability of whole blood serum to enhance binding of fibronectin was abolished by phospholipase B. These results indicate that lysophosphatidic acid derived from platelets is the principal component in whole blood serum that is active in the fibronectin binding assay. 1-oleoyl lysophosphatidic acid, 20-200 nM, was as active as 0.1-0.2% whole blood serum. The stimulatory effect of lysophosphatidic acid on the binding of fibronectin or the amino-terminal 70-kD fragment of fibronectin was rapid, sustained, and lost upon removal of lysophosphatidic acid. The stimulatory effect on binding could not be duplicated by bradykinin, platelet-activating factor, bombesin, or a peptide agonist of the thrombin receptor. Enhanced binding of the 70-kD fragment was due to increases in both the number and affinity of binding sites. Enhanced binding and assembly of fibronectin correlated with changes in cell shape and actin-containing cytoskeleton. The binding sites for fibronectin on lysophosphatidic acid-stimulated cells, as assessed by fluorescence, video, and scanning electron microscopy, were on areas of cell membrane containing numerous filopodia that extended between cells or between cells and substratum. These observations suggest that lysophosphatidic acid functions as a powerful and specific modulator of cell shape and early matrix assembly during wound healing.

Actin Cytoskeleton↗
PubMed1994

Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) has been shown to stimulate cell proliferation after vascular injury. The mitogenic activity of bFGF requires interactions with both a high affinity receptor and a cell-surface heparan sulfate proteoglycan. We tested the ability of platelet factor 4 (PF 4) and other platelet heparin-binding proteins to modulate bFGF-stimulated [3H]thymidine incorporation into fibroblasts. The supernatant of thrombin-stimulated platelets contained an inhibitor of bFGF-induced mitogenesis; this activity coeluted with PF 4 upon gel filtration, heparin-agarose, and ion-exchange chromatography. Purified thrombospondin and beta-thromboglobulin did not inhibit the mitogenic activity of bFGF. PF 4 inhibited the activity of 5 pM bFGF with 50% inhibitory concentration of 75 nM. Purified PF 4 also inhibited the basal incorporation of [3H]thymidine into 3T3 fibroblasts and the increased [3H]thymidine incorporation occurring after wounding of a cell monolayer. PF 4 did not affect the mitogenic activity of serum. Inhibition of bFGF activity by PF 4 could be overcome by exogenous heparin or chondroitin-4-sulfate, suggesting that inhibition of mitogenesis is caused by binding of PF 4 to cell-surface glycosaminoglycans. These results indicate that an important role of PF 4 released at sites of vascular injury and platelet activation is to control cellular proliferation caused by the release of bFGF from ruptured cells.

3T3 Cells↗
PubMed1993

Alteration of vitronectin. Characterization of changes induced by treatment with urea.

Vitronectin circulates in blood as a 70-kDa monomer that interacts with complexes generated in the terminal steps of the coagulation and complement cascades. Vitronectin complexed to thrombin-antithrombin or C5b-9 is conformationally altered as evidenced by enhanced reactivity with monoclonal antibody 8E6 and binding to heparin; these same alterations also occur when vitronectin is treated with urea (Tomasini, B. R., and Mosher, D.F. (1988) Blood 72, 903-912; Høgåsenk, K., Molnes, T.E., and Harboe, M. (1992) J. Biol. Chem. 267, 23076-23082). We have modified the purifications of native and urea-treated vitronectin to better control conformational state and characterized the alterations induced by urea. After treatment with N-ethylmaleimide to prevent formation of disulfide-linked multimers, purification in 8 M urea, and dialysis against physiological saline, vitronectin was largely oligomeric (approximately 800 kDa) as assessed by gel filtration and polyacrylamide gel electrophoresis in the absence of sodium dodecyl sulfate. Oligomeric urea-treated vitronectin reacted more strongly with the 8E6 antibody, bound biotinylated heparin more strongly, and neutralized the anticoagulant activity of heparin better than monomeric altered vitronectin or native vitronectin. After incubation with urea at 25 degrees C, native vitronectin, treated during purification with dithionitrobenzoic acid to force free sulfhydryls to intramolecular disulfides, exhibited increased reactivity with antibody 8E6, increased binding to heparin, and oligomerization. In addition, incubation in urea caused rearrangement of disulfides as assessed by loss of the light chain of two-chain vitronectin. The transition for these effects occurred between 2 and 4 M urea. Thus, an irreversible conformational alteration occurs upon treatment of vitronectin with urea, resulting in oligomers that bind avidly to heparin.

Antibodies↗
PubMed1993

Protein kinase C modulation of fibronectin matrix assembly.

Fibroblasts have cell surface sites that mediate the assembly of fibronectin (Fn) into the extracellular matrix. Treatment of fibroblasts with kinase inhibitors (ML-7, H7, HA1004, calphostin C, and staurosporine) resulted in the rapid decrease in the binding of 125I-labeled plasma Fn and iodinated amino-terminal fragments of Fn. The dose responses of the four inhibitors suggest that the target kinase is protein kinase C (PKC) rather than the cyclic AMP- or cyclic GMP-dependent kinases. Three different fibroblastic cells were similarly affected. The inhibition was rapid and reversible and could not be overcome by increasing concentrations of Fn. Treatment of fibroblasts with phorbol esters and other agents that activate PKC resulted in increased amounts of 125I-labeled Fn binding to the cell surface. These results imply that Fn matrix assembly is modulated by PKC-mediated phosphorylation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Kinetics of inactivation of alpha-thrombin by plasminogen activator inhibitor-1. Comparison of the effects of native and urea-treated forms of vitronectin.

Kinetic studies are presented which show that native human vitronectin, but not urea-treated vitronectin, accelerates the inactivation of human alpha-thrombin by human plasminogen activator inhibitor-1 (PAI-1). We demonstrate that although urea-treated vitronectin binds PAI-1 with an affinity greater than that of native vitronectin, it does not accelerate the rate of inactivation of alpha-thrombin by PAI-1. We present evidence to suggest that the inability of urea-treated vitronectin to accelerate the reaction between alpha-thrombin and PAI-1 results at least in part from the inability of urea-treated vitronectin to bind to alpha-thrombin. The accelerated reaction between PAI-1 and alpha-thrombin can be accounted for by the formation of a tight complex between native vitronectin and PAI-1 that reacts in a saturable manner (Kd = 75 nM) with alpha-thrombin. The second-order rate constant (kI/Kd) for the reaction of the native vitronectin-PAI-1 complex with alpha-thrombin (1.64 x 10(5) M(-)-1 s-1) is 270-fold greater than the second-order rate constant for the reaction in the absence of vitronectin (610 m-1 s-1). The increase in the second-order rate constant is largely due to an increase in the affinity of alpha-thrombin for the native vitronectin-PAI-1 complex, as reflected by a greater than 25-fold reduction in the dissociation constant (Kd) observed for the vitronectin-PAI-1 complex relative to that of uncomplexed PAI-1.

Blood Proteins↗
PubMed1993

Thrombospondin is a tight-binding competitive inhibitor of neutrophil elastase.

Thrombospondin, a glycoprotein of three identical disulfide-bonded subunits, is a constituent of platelet alpha-granules and a variety of normal and transformed cells and binds to cell surfaces and becomes incorporated into extracellular matrix. It has been implicated in processes such as wound healing and tumor growth and metastasis. In addition, thrombospondin was shown recently to be an inhibitor of the fibrinolytic enzyme, plasmin. In the cause of studying the effects of thrombospondin on other serine proteinases, we found that thrombospondin binds neutrophil elastase in an active-site-dependent manner and competitively inhibits the activity of the enzyme. In a competitive binding assay, neutrophil elastase bound to thrombospondin with a dissociation constant of 17 +/- 7 nM, expressed per mole of thrombospondin trimer, or 52 +/- 20 nM, expressed per mole of thrombospondin subunit. In kinetic studies of the inhibition of the amidolytic activity of neutrophil elastase by thrombospondin, 2.7 +/- 0.3 mol of elastase interacted with 1 mol of thrombospondin trimer with a site-binding constant of 57 +/- 13 nM. Lower limits for the on rate constant of 5 x 10(6) M-1 s-1 and off rate constant of 0.27 s-1 were established. Affinity of binding of neutrophil elastase to thrombospondin was sensitive to ionic strength and calcium ions. Thrombospondin was cleaved by neutrophil elastase, but the site(s) of the limited cleavage are independent of the competitive inhibition of elastase activity by thrombospondin. Neutrophil elastase inactivated with phenylmethylsulfonyl fluoride did not compete with active elastase for binding to thrombospondin, implying that a functional active site is important for the interaction of elastase with thrombospondin. Thrombospondin protected fibronectin from cleavage by neutrophil elastase. In summary, the binding of neutrophil elastase to thrombospondin is tight, reversible, and close enough to the active site of elastase to exclude small synthetic tripeptidyl p-nitroanilide substrates and macromolecular protein substrates. Two potential reactive centers that may be involved in binding elastase have been identified in the calcium-binding type 3 domains of thrombospondin. Neutrophil elastase is the enzyme primarily responsible for degrading and solubilizing connective tissue during inflammatory processes. These findings suggest a previously unsuspected mechanism for regulation of elastase activity at inflammatory sites.

Amino Acid Sequence↗
PubMed1993

Assembly of fibronectin molecules with mutations or deletions of the carboxyl-terminal type I modules.

Fibronectin is a large modular protein that is assembled into fibrils in a stepwise process that involves the binding of soluble fibronectin to the cell surface and formation of fibronectin multimers that are stabilized by disulfides. Fibronectin contains two types of disulfide-containing repeat modules, types I and II. The type I modules form units that mediate binding to assembly sites (I-1 through I-5), mediate binding to gelatin (I-6 through I-9 plus the type II modules), or have no known function other than fibrin binding (I-10 through I-12). All type I modules contain four cysteines that are disulfide-linked in a 1-3, 2-4 arrangement, except for I-12 that contains six cysteines disulfide-bonded in an unknown arrangement. I-12 contains the consensus sequence Cys-Xaa-Yaa-Cys found in a number of proteins involved in disulfide exchange reactions [Holmgren, A. (1985) Annu. Rev. Biochem. 54, 237; Boniface, J. J., & Reichert, L. E., Jr. (1990) Science 247, 61]. We explored the role of I-12 and adjacent type I modules of fibronectin in matrix assembly. We generated mutant fibronectins in which the second and sixth or fifth and sixth cysteine residues in I-12 were changed to serines (CS mutants) or that contained deletions of the 12th (delta 12) or 10th through 12th (delta 10-12) type I modules. Expression of I-12 as a fusion protein with the gelatin binding part of fibronectin indicated that this module folds independently and that the most likely disulfide pairing is 1-4, 2-6, 3-5.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Adhesion of Staphylococcus aureus to surface-bound platelets: role of fibrinogen/fibrin and platelet integrins.

Platelets adhering to artificial or biologic surfaces have been implicated in the pathogenesis of catheter infections or endocarditis; however, the ligands involved in Staphylococcus aureus interaction with adherent platelets remain incompletely understood. Radiolabeled S. aureus Cowan I were incubated with purified platelets adherent to polymethylmethacrylate (PMMA) coverslips and washed, and adhesion was determined. Platelets promoted adhesion of S. aureus approximately 30-fold compared with adhesion to albumin-PMMA. In the presence of both plasma (1% vol/vol) and platelets, adhesion was extensively promoted, with 30% (of inoculated) S. aureus adherent (150-fold increase). Platelet pretreatment with anti-GPIIb/IIIa monoclonal antibodies or inhibitors of platelet activation decreased plasma-enhanced adhesion, suggesting a role of platelet activation in S. aureus adhesion. Plasma-enhanced adhesion was sensitive to thrombin antagonists, proteinase inhibitors, heparin, or antifibrinogen antibodies, indicating that fibrinogen/fibrin is necessary for bridging between adherent platelets and S. aureus. In conclusion, S. aureus adhesion to immobilized platelets may play a role in the pathogenesis of invasive bloodstream infections or endocarditis.

Bacterial Adhesion↗
PubMed1993

Lysophosphatidic acid enhances fibronectin binding to adherent cells.

1-Oleoyl lysophosphatidic acid (LPA) enhanced binding of 125I-labeled fibronectin by cultured MG-63 osteosarcoma cells and human fibroblasts in monolayer cultures up to threefold over control levels. For osteosarcoma cells, LPA was minimally active at 0.1 ng/mL (0.2 nmol/L) and reached maximal activity at 10 ng/mL (20 nmol/L). Increased binding was evident within 10 minutes of treatment of cycloheximide-treated cells with LPA and was due to an increase in the number of fibronectin binding sites. LPA also increased the binding of a fragment containing the 70-kDa amino-terminal region of fibronectin that is primarily responsible for the reversible binding of fibronectin to matrix assembly sites on cell surfaces. Removal of LPA resulted in prompt return of fibronectin binding to baseline levels. These results indicate that LPA is an important enhancer of fibronectin-rich matrix deposition by cultured cells, and it may be the active component in serum and lipoprotein fractions that is responsible for enhancing fibronectin deposition.

Binding Sites↗
PubMed1993

Elevated levels of bronchoalveolar lavage vitronectin in hypersensitivity pneumonitis.

Vitronectin is an adhesive glycoprotein that is present in plasma and the extracellular matrix. Hypersensitivity pneumonitis (HP) is characterized by pulmonary inflammation and damage to the extracellular matrix. Perhaps reflecting this, fibronectin has been found to be elevated in the lower respiratory tract of subjects with HP. Vitronectin, like fibronectin, binds to both extracellular matrix components and cells and may mediate tissue remodeling. Thus, it was investigated whether vitronectin might be increased in bronchoalveolar lavage (BAL) fluid of patients with HP. Vitronectin and, for comparison, fibronectin were measured in BAL fluid from 16 patients with HP and nine healthy control subjects by enzyme-linked immunosorbent assay. Vitronectin was significantly increased in the HP group (658.4 +/- 121.8 ng/ml) compared with the controls (58.4 +/- 11.1 ng/ml, p < 0.001) and was found to be positively correlated with fibronectin. Patients whose last antigenic exposure was 4 or fewer days before the BAL had statistically significantly higher BAL vitronectin and fibronectin than did patients whose last exposure was 5 or more days before the BAL. The serum vitronectin levels did not differ. There was no significant relationship between the lavage fluid vitronectin and fibronectin levels and the BAL cell profile in HP. This study confirms that vitronectin, like fibronectin, is a normal constituent of the lower respiratory tract, and demonstrates that vitronectin is elevated in the lower respiratory tract of patients with HP and may play a role in tissue remodeling and fibrosis in this disease.

Adult↗
PubMed1992

Modulation of fibrinolysis by thrombospondin.

Thrombospondin is a large, trimeric glycoprotein secreted by activated platelets and growing cells. Thrombospondin copolymerizes with fibrin during blood coagulation and deposits in extracellular matrix. We found that thrombospondin is a slow (rate constant approximately 6.3 x 10(3) M-1 sec-1), tight-binding (Kd < 10(-9) M) inhibitor of plasmin as determined by loss of amidolytic activity, loss of ability to degrade fibrinogen, and decreased lysis zones in fibrin plate assays (Biochemistry 31: 265-269, 1992). Thrombospondin also slowly inhibits urokinase plasminogen activator. The lysis zone when urokinase is put on fibrin plates made from whole plasma is less if thrombospondin is present. The stoichiometry of inhibition is approximately one mole plasmin:one mole thrombospondin trimer, a somewhat surprising result considering the trimeric nature of thrombospondin. These results indicate that thrombospondin is an important regulator of fibrinolysis and degradation of extracellular matrix, particularly when these processes are initiated by urokinase and even when other inhibitors of fibrinolysis are present.

Animals↗
PubMed1992

The ex vivo effect of preadsorbed vitronectin on platelet activation.

The activation of ex vivo canine platelets by preadsorbed vitronectin (VN) was sensitive not only to the polymer substrate utilized but also to the adsorption conditions employed. Lower levels of maximal platelet deposition were obtained for VN-coated silicone rubber (SR) than for other VN-coated substrates with comparable levels of adsorbed VN, but this effect was diminished with increased residence time of VN on the SR surface. Submonolayer and monolayer surface concentrations of VN elicited similar maximal levels of platelet deposition at both short (less than 3 h) and long (greater than 12 h) residence times, but thrombi were larger and more dense for the submonolayer surface concentrations. VN was also more effective in forming thrombi when adsorbed sequentially before albumin instead of after albumin. To further examine these differences in the nature of adsorbed VN between substrates and adsorption conditions, sodium dodecyl sulfate (SDS) elutability measurements and Fourier transform infrared spectroscopy with attenuated total reflectance optics (FTIR-ATR) evaluations of the adsorbed protein were performed. An SDS solution was able to remove a greater percentage of the VN which was adsorbed to a submonolayer than a monolayer surface concentration when SDS displacement was initiated immediately after adsorption was terminated. However, if the adsorbed protein was allowed to reside on the surface for a length of time before the introduction of the SDS displacing media, a greater percentage of the monolayer surface concentration was removed. The submonolayer surface concentration may be better able to increase its strength of contact with the surface during the added residence time than the monolayer surface concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗
PubMed1992

Thrombospondin is a slow tight-binding inhibitor of plasmin.

Thrombospondin is a multifunctional glycoprotein of platelet alpha-granules and a variety of growing cells. We demonstrate that thrombospondin is a slow tight-binding inhibitor of plasmin as determined by loss of amidolytic activity, loss of ability to cleave fibrinogen, and decreased lysis zones in fibrin plate assays. Stoichiometric titrations indicate that approximately 1 mol of plasmin interacts with 1 mol of thrombospondin, an unexpected result considering the trimeric nature of thrombospondin. Plasmin in a complex with streptokinase or bound to epsilon-aminocaproic acid is protected from inhibition by thrombospondin, thereby implicating the lysine-binding kringle domains of plasmin in the inhibition process. Thrombospondin also inhibits urokinase plasminogen activator, but more slowly than plasmin, stimulates the amidolytic activity of tissue plasminogen activator, and has no effect on the amidolytic activity of alpha-thrombin or factor Xa. These results, therefore, identify thrombospondin as a new type of serine proteinase inhibitor and potentially important regulator of fibrinolysis.

Blood Platelets↗
PubMed1992

Endothelial cell adhesion on polyurethanes containing covalently attached RGD-peptides.

Peptides based on cell-adhesive regions of fibronectin, Arg-Gly-Asp-Ser (RGDS), and vitronectin, Arg-Gly-Asp-Val (RGDV), were covalently bound to a polyurethane backbone via amide bonds. Nuclear magnetic resonance (NMR) and Fourier-transform infrared (FTIR) spectroscopies were used to monitor the reactions. The amount of grafted peptide was determined by amino acid analysis. X-ray photoelectron spectroscopy (XPS) suggested the presence of the grafted peptide at the polymer-air interface in vacuo. Dynamic contact angle analysis showed that, in water, the peptide-grafted polyurethane surfaces were more polar than the underivatized polyurethane indicating enrichment of peptide groups at the surface. The attachment and spreading of human umbilical vein endothelial cells (HUVECs) on the underivatized and peptide-grafted polyurethanes was investigated. The GRGDSY- and GRGDVY-grafted substrates supported cell adhesion and spreading even without serum in the culture medium. The GRGDVY-grafted substrate supported a larger number of adherent cells and a higher extent of cell spreading than the GRGDSY-grafted substrate. These RGD-containing peptide-grafted polyurethane copolymers may be useful in providing an easily prepared cell-adhesive substrate for various biomaterial applications.

Amino Acids↗
PubMed1992

Assembly of extracellular matrix.

A great challenge in understanding how different extracellular matrices assemble is to sort through the vast number of possible interactions between and among matrix molecules. The most profound insights are likely to come from patients with defined defects of matrix molecules and the use of transgenic mice or other experimental technologies that mimic the complexity of the human system.

Amino Acid Sequence↗