Abstract
Integrins play a vital role in cellular responses to environmental cues during early-stage cell-substrate interaction. We describe physiologically relevant cell anchorage to collagen substrates that present different affinity cell-recognition motifs, to provide experimental tools to assist in understanding integrin binding. Using different cell types and recombinant integrin α1-I-domains, we found that cellular response was highly dependent on collagen type, origin and EDC-crosslinking status, as well as on the integrin class and species of origin. This comprehensive study establishes selectivity amongst the four collagen-binding integrins and species-specific properties that together may influence choice of cell type and receptor in different experimental settings. This work offers key guidance in selecting of the correct cellular model for the biological testing of collagen-based biomaterials.
Highlights
Natural extracellular matrix (ECM) contains a mixture of proteins and polysaccharides that display biochemical cues which influence cell behaviour
The results showed that the binding properties of transfected C2C12 cells to collagens depend on the identity of inserted integrin
Using different cell types and recombinant integrin a1-I-domains, we found that cellular response was highly dependent on collagen type, origin and ethyl-3-(3-dimethylaminopropyl)-carbo diimide hydrochloride (EDC)-crosslinking status, as well as on the integrin class and species of origin
Summary
Natural extracellular matrix (ECM) contains a mixture of proteins and polysaccharides that display biochemical cues which influence cell behaviour. ECM components possess different adhesive motifs with diverse affinities towards a variety of cell recognition receptors Despite this complex tissue composition, for many years, collagen (in forms including gels, scaffolds and membranes) has been a commonly used biomaterial due to its biocompatibility, biodegradability and low immunogenicity, together with its ability to form fibres with high tensile strength [2,3,4,5]. Col II is the chief element in articular cartilage (approximately 60% of the dry weight of this tissue) [2,9] while Col III is an important component of reticular fibres, where it is commonly found alongside Col I [10], for example in skin and blood vessel walls These collagens have been used, alone or in combination, for the design of bio scaffolds [2,3,5]. The structural diversity observed in different Col types affects their adhesive motifs which may in turn have impact on their cell-substrate interactions via integrins [6,7]
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