Collagen Assembly at the Cell Surface: Dogmas Revisited

Area of Science:

• Cell biology
• Biochemistry
• Tissue engineering

Background:

• Extracellular matrix (ECM) composition, organization, and stiffness are crucial for tissue homeostasis.
• Fibronectin (FN) and fibrillar collagens are key ECM components, with collagens forming persistent scaffolds in regenerating tissues.
• Historically, cell anchorage to collagen was considered indirect via FN, and collagen fibrillogenesis was thought to require an FN matrix.

Purpose of the Study:

• To re-evaluate the absolute dependence on fibronectin (FN) for cell-mediated collagen fibrillogenesis.
• To summarize evidence supporting the role of collagen-binding integrins in nucleating and supporting collagen fibrillogenesis.
• To highlight the importance of characterizing the full integrin repertoire, including collagen receptors.

Main Methods:

• Review and summarization of existing in vitro and in vivo data.
• Analysis of the role of specific collagen-binding integrins (α1β1, α2β1, α10β1, α11β1).
• Investigation of cell anchorage mechanisms to collagen matrices.

Main Results:

• Four collagen-binding integrins enable direct cell anchorage to monomeric fibrillar collagens.
• The binding of these integrins to mature collagen matrices is dependent on the availability of binding sites.
• Collagen-binding integrins are capable of nucleating and supporting collagen fibrillogenesis independently of FN.

Conclusions:

• The established dogma of fibronectin (FN) dependence for cell-mediated collagen fibrillogenesis needs re-evaluation.
• Collagen-binding integrins are sufficient for initiating and supporting collagen fibrillogenesis, both in vitro and in vivo.
• Direct cell-collagen interactions via integrins play a significant role in ECM remodeling and tissue regeneration.