Mimicking the Extracellular Matrix: The Intersection of Matrix Biology and Biomaterials
CHAPTER 4: Matrix Biology: Structure and Assembly of Laminin-Rich Matrices
Published:18 Nov 2015
Kevin J. Hamill, Susan B. Hopkinson, Natalie M. E. Hill, Jonathan C. R. Jones, 2015. "Matrix Biology: Structure and Assembly of Laminin-Rich Matrices", Mimicking the Extracellular Matrix: The Intersection of Matrix Biology and Biomaterials, Gregory A Hudalla, William L Murphy
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The extracellular matrix (ECM) has profound effects on cell behavior, with consequent influence on the regulation of development, organogenesis and tissue remodeling, maintenance of stem cells, tissue integrity and homeostasis, and angiogenesis. Moreover, matrix changes not only occur during disease, but reorganization and the laying down of new matrix is also a critical mechanism underlying pathogenesis of numerous syndromes.
The ECM is a complex structure and it would be impossible to provide a comprehensive review of matrix proteins in a single chapter. Hence, we will restrict our review to laminins. Laminins are heterotrimeric glycoproteins secreted by a variety of cell types and incorporated, along with other proteins, into specialized ECM structures, termed basement membranes (BMs) (Figure 4.1).1–3 BMs are found beneath epithelia and endothelia and surround muscles and nerves. Laminin expression is dependent not only on cell type but also on context.4 Moreover, domain composition may be modified as a result of alternative splicing or the structure may be changed following post-translational processing. In addition, laminin matrices may exhibit different assembly forms, depending on whether a tissue is quiescent or undergoing remodeling. The diversity in laminin matrix structure would imply that they exhibit a range of functions, evidence for which is discussed below. Most importantly, laminins provide the point of interaction between cells and their extracellular microenvironment. The laminins therefore are in an ideal location to influence directly cell behavior, which they do through two main mechanisms: (1) interaction with cell-surface receptors leading to modification of downstream signaling events; or (2) through physical modification of cellular substrates. We begin our review by detailing laminin nomenclature and the structure of laminin subunits.