The structure of nanoscale 3D oriented matrices has collagen as its core material. However these matrices are considerably more complex in practice and may have a number of other biological materials outlined below.
Collagens are a family of over 25 proteins that share a triple helical structure formed from three a-chains. The various types of collagen exhibit differences such as structure, splice variants, additional non-helical domains and function. The most abundant collagens are fibril forming types I, II, III, V, and XI. The process of fibril formation is only partially understood even after years of debate. The specific nature of fibril formation is dependent on factors such as cleavage of collagen propeptide sequences and the formation of covalent cross-links. Fibril-forming collagens can spontaneously aggregate to form organized fibrils. Fibril diameter varies from 30nm to 500nm.
There are nonfibrillar collagens such as type IV, which is the principal component of basement membranes. They integrate other ECM molecules such as laminin into characteristic flat sheet aggregates. There are fibril-associated collagens with interrupted triple helices such as types IX, XII, XIV, XVI, XIX, and XX, typically located on the surface of collagen fibrils. Type VI is a microfibrillar collagen forming a network of fine filaments throughout connective tissues. Short chain collagens, types X and VIII, form hexagonal networks.
Collagens are a complex family of molecules that interact with each other and other ECM molecules to provide a wide range of structures and functions throughout the body. Examples include interactions with cells to influence adhesion, growth and differentiation and with growth factors and cytokines to influence tissue development.
Fibrin, unlike collagen, is not a protein associated with mature tissue structures, but rather a temporary repair stage ECM component. It functions to form a provisional matrix after damage that is later replaced by cellular activity. This feature makes it a suitable candidate for delivery of cells to damaged tissues. As an example of one of its many uses, fibrin polymerizes in the presence of thrombin to form a dense meshwork of fibers which is used to form ‘‘fibrin glue’’, useful for anchoring skin grafts. Matrices of fibrin alone lack the mechanical strength seen with other protein scaffolds.
Fibronectin, like collagen, is a prominent constituent of extracellular matrices but like fibrin, it is also involved in tissue repair responses. This combination of features makes it a particularly valuable candidate for tissue-engineered approaches. Indeed, it is considered to be the first cell scaffold element of the provisional matrix laid down in early wound repair by fibroblasts throughout the body. It also influences cell proliferation and differentiation, cytoskeletal organization, gene expression, cell cycle progression, and cell survival. Many of its properties have been harnessed to create tissue-engineering scaffolds that can confer alignment and deliver cells and soluble factors to sites of repair.
Laminin is a self-polymerizing extracellular matrix protein which plays a variety of roles for many cell types. These roles include survival, proliferation, migration, differentiation, apoptosis and in particular the instruction of neural cells during both tissue development and regeneration. It is well accepted that laminin signaling depends on its self-polymerization, which naturally occurs on cell membranes. Because laminin is key in determining cell fate, it is important to be able to produce artificial laminin matrices that can mimic the polymers produced by cells in vivo.
Silk proteins are naturally occurring biomaterials that come predominantly from silk worms and spiders. They have been shown to have the potential as biomimetic proteins in therapeutic roles. Their primary attribute is high tensile strength, which far exceeds that of collagen and approaches that of high tensile steel. Genetic engineering has enabled large scale synthetic production of various types of silk.
- Adopted from R. A. Brown and J. B. Phillips, International Review of Cytology, 262, 2007.
- M. Barroso et al. J. Biol. Chem., 283, Issue 17, 2008.