In the process of matrix assembly, multivalent extracellular matrix (ECM) proteins are induced to self-associate and to interact with other ECM proteins to form fibrillar networks. Matrix assembly is usually initiated by ECM glycoproteins binding to cell surface receptors, such as fibronectin (FN) dimers binding to α5β1 integrin. Receptor binding stimulates FN self-association mediated by the N-terminal assembly domain and organizes the actin cytoskeleton to promote cell contractility. FN conformational changes expose additional binding sites that participate in fibril formation and in conversion of fibrils into a stabilized, insoluble form. Once assembled, the FN matrix impacts tissue organization by contributing to the assembly of other ECM proteins. Here, we describe the major steps, molecular interactions, and cellular mechanisms involved in assembling FN dimers into fibrillar matrix while highlighting important issues and major questions that require further investigation.
Background: Cell behavior is affected by changes in extracellular matrix stiffness during disease progression. Results: Fibronectin matrix assembly is inhibited on soft substrates but can be restored by manipulating cell-fibronectin binding or by partially unfolding substrate fibronectin. Conclusion: On soft substrates, cells are deficient in integrin-fibronectin bond strength and therefore cannot induce fibronectin conformational changes required for assembly. Significance: Rigidity-dependent changes in fibronectin conformation provide a novel mechanism for mechanotransduction.
Suitable structure characterization is assisted through the use of mass spectrometry. Polymer fragmentation can be achieved in many ways including application of heat and ionizing radiation. MALDI MS allows routine analysis of polymers allowing identification of several repeat units. Graphite as a matrix allows higher mass ions to be created with less interfering ion fragments formed in comparison to more utilized matrix materials.
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