Collagen is the most abundant protein in animals. This fibrous, structural protein comprises a right-handed bundle of three parallel, left-handed polyproline II-type helices. Much progress has been made in elucidating the structure of collagen triple helices and the physicochemical basis for their stability. New evidence demonstrates that stereoelectronic effects and preorganization play a key role in that stability. The fibrillar structure of type I collagen—the prototypical collagen fibril—has been revealed in detail. Artificial collagen fibrils that display some properties of natural collagen fibrils are now accessible using chemical synthesis and self-assembly. A rapidly emerging understanding of the mechanical and structural properties of native collagen fibrils will guide further development of artificial collagenous materials for biomedicine and nanotechnology.

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Collagen Structure and Stability

Fibronectin (FN) mediates a wide variety of cellular interactions with the extracellular matrix (ECM) and plays important roles in cell adhesion, migration, growth and differentiation ( [Mosher, 1989][1]; [Carsons, 1989][2]; [Hynes, 1990][3]; [Yamada and Clark, 1996][4]). FN is widely expressed by

/pdf/fibronectin-at-a-glance-h6djik8qk2.pdf

Fibronectin at a glance.

Extracellular matrix structure.

Collagen fibrils in the extracellular matrix allow connective tissues such as tendon, skin and bone to withstand tensile forces. The fibrils are indeterminate in length, insoluble and form elaborate three-dimensional arrays that extend over numerous cell lengths. Studies of the molecular basis of collagen fibrillogenesis have provided insight into the trafficking of procollagen (the precursor of collagen) through the cellular secretory pathway, the conversion of procollagen to collagen by the procollagen metalloproteinases, and the directional deposition of fibrils involving the plasma membrane and late secretory pathway. Fibril-associated molecules are targeted to the surface of collagen fibrils, and these molecules play an important role in regulating the diameter and interactions between the fibrils.

/pdf/procollagen-trafficking-processing-and-fibrillogenesis-5bvje29zys.pdf

Procollagen trafficking, processing and fibrillogenesis

Collagen is the oldest and most abundant extracellular matrix protein that has found many applications in food, cosmetic, pharmaceutical, and biomedical industries First, an overview of the family of collagens and their respective structures, conformation, and biosynthesis is provided The advances and shortfalls of various collagen preparations (eg, mammalian/marine extracted collagen, cell-produced collagens, recombinant collagens, and collagen-like peptides) and crosslinking technologies (eg, chemical, physical, and biological) are then critically discussed Subsequently, an array of structural, thermal, mechanical, biochemical, and biological assays is examined, which are developed to analyze and characterize collagenous structures Lastly, a comprehensive review is provided on how advances in engineering, chemistry, and biology have enabled the development of bioactive, 3D structures (eg, tissue grafts, biomaterials, cell-assembled tissue equivalents) that closely imitate native supramolecular assemblies and have the capacity to deliver in a localized and sustained manner viable cell populations and/or bioactive/therapeutic molecules Clearly, collagens have a long history in both evolution and biotechnology and continue to offer both challenges and exciting opportunities in regenerative medicine as nature's biomaterial of choice

/pdf/the-collagen-suprafamily-from-biosynthesis-to-advanced-19x5x1lvm2.pdf

The Collagen Suprafamily: From Biosynthesis to Advanced Biomaterial Development

Measured by ultra-slow scanning calorimetry and isothermal circular dichroism, human lung collagen monomers denature at 37°C within a couple of days. Their unfolding rate decreases exponentially at lower temperature, but complete unfolding is observed even below 36°C. Refolding of full-length, native collagen triple helices does occur, but only below 30°C. Thus, contrary to the widely held belief, the energetically preferred conformation of the main protein of bone and skin in physiological solution is a random coil rather than a triple helix. These observations suggest that once secreted from cells collagen helices would begin to unfold. We argue that initial microunfolding of their least stable domains would trigger self-assembly of fibers where the helices are protected from complete unfolding. Our data support an earlier hypothesis that in fibers collagen helices may melt and refold locally when needed, giving fibers their strength and elasticity. Apparently, Nature adjusts collagen hydroxyproline content to ensure that the melting temperature of triple helical monomers is several degrees below rather than above body temperature.

https://www.pnas.org/content/pnas/99/3/1314.full.pdf

E. Leikina

Papers

Type I collagen is thermally unstable at body temperature.