Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research

Figure 3

Laminins: a model system to investigate roles of molecular complexity of natural matrix molecules. Natural extracellular matrix molecules are very large and complex molecules, often composed of more than one polypeptide chain (collagens have 3 chains, laminins have 3 chains, and fibronectin has 2 chains) and multiple domains with distinct adhesive and geometrical properties. Mutations in either chains or domains often result in severe pathology. Apparently, such molecular complexity developed during evolution for a reason, and natural ECM molecules have more function, compared to small adhesive peptides. However, it is not easy to establish roles for each specific domain and structure of the natural large ECM molecules. Family of laminins, due to their molecular versatility, is a perfect model system to investigate reasons for functional complexity of matrix molecules. Laminins are the natural adhesion ligands for many stem cell types, like embryonic stem cells (ESC), hematopoietic stem cells, sperm stem cells, and probably many others. Due to unique composition of three heterogeneous chains, each of which can be varied, cell adhesion domains undergoing natural proteolytic maturation and, therefore, change in affinity and specificity, availability of conditional knockout models, and mutated proteins in laminin family are an excellent system to investigate reasons for molecular complexity of natural matrix molecules. Laminins are large, heterotrimeric molecules that comprise one α, one β, and one γ chain. Size of laminin trimer varies from 400 to 1000 kDa. Five α (α1–α5), four β (β1–β4), and three γ (γ1–γ3) chains are known in mammals. Laminin-521 (LM-521) consists of α5, β2, and γ1 chains. The molecule in the figure represents the cross-shaped laminin isoform; however, some laminin isoforms have truncated shapes: Y-like or rod-like shape. The α1, α2, α3B, and α5 trimers are cross-shaped, while the α3A and α4 trimers are Y-shaped or rod-shaped. Short arms of laminins (N-terminal parts of α, β, and γ chains) can bind other laminins short arms and other ECM proteins. Laminins in solution are capable of self-assembly via N-terminal short arms in the presence of calcium.