The collagen superfamily includes more than fifty collagen and/or collagen-like proteins with fibril-forming collagen type I being the most abundant protein within the extracellular matrix. Collagen type I plays a crucial role in a variety of functions, it has been associated with many pathological conditions and it is widely used due to its unique properties. One unique nano-scale characteristic of natural occurring collagen type I fibers is the so-called D-band periodicity, which has been associated with collagen natural structure and properties, while it seems to play a crucial role in the interactions between cells and collagen and in various pathological conditions. An accurate characterization of the surface and structure of collagen fibers, including D-band periodicity, on collagen-based tissues and/or (nano-)biomaterials can be achieved by Atomic Force Microscopy (AFM). AFM is a scanning probe microscope and is among the few techniques that can assess D-band periodicity. This review covers issues related to collagen and collagen D-band periodicity and the use of AFM for studying them. Through a systematic search in databases (PubMed and Scopus) relevant articles were identified. The study of these articles demonstrated that AFM can offer novel information concerning D-band periodicity. This study highlights the importance of studying collagen D-band periodicity and proves that AFM is a powerful tool for investigating a number of different properties related to collagen D-band periodicity.
Keywords: Atomic Force Microscopy (AFM); D-band; D-periodicity; D-spacing; biomaterials; collagen; mechanical properties.