Collagen is the most abundant protein in animals, forming a right-handed triple helix composed of three parallel, left-handed polyproline II-type helices. Recent studies have elucidated the structural and physicochemical basis for collagen stability, highlighting the roles of stereoelectronic effects and preorganization. Type I collagen, the prototypical collagen fibril, has been extensively studied, revealing its fibrillar structure and the potential of artificial collagen fibrils for biomedical and nanotechnology applications. Collagen's triple helix structure is stabilized by interstrand hydrogen bonds and the repeating XaaYaaGly sequence, with proline and hydroxyproline residues playing key roles. The stability of collagen is influenced by the arrangement of these residues, with proline-rich regions promoting triple-helix nucleation. Mutations in collagen can disrupt this structure, leading to diseases like osteogenesis imperfecta. The hydroxylation of proline residues by prolyl 4-hydroxylase is essential for collagen formation. Hyp (hydroxyproline) stabilizes the triple helix through stereoelectronic effects, while substitutions like fluoroproline can also influence stability. The structure of collagen fibrils is hierarchical, with microfibrils assembling into larger fibrils. The mechanical properties of collagen fibrils, including their strength and elasticity, are influenced by factors such as cross-linking and hydration. Synthetic collagen-like materials have been developed using chemical synthesis and self-assembly, offering potential applications in biomaterials and nanotechnology. The study of collagen structure and stability continues to provide insights into its biological functions and potential uses in medicine and materials science.Collagen is the most abundant protein in animals, forming a right-handed triple helix composed of three parallel, left-handed polyproline II-type helices. Recent studies have elucidated the structural and physicochemical basis for collagen stability, highlighting the roles of stereoelectronic effects and preorganization. Type I collagen, the prototypical collagen fibril, has been extensively studied, revealing its fibrillar structure and the potential of artificial collagen fibrils for biomedical and nanotechnology applications. Collagen's triple helix structure is stabilized by interstrand hydrogen bonds and the repeating XaaYaaGly sequence, with proline and hydroxyproline residues playing key roles. The stability of collagen is influenced by the arrangement of these residues, with proline-rich regions promoting triple-helix nucleation. Mutations in collagen can disrupt this structure, leading to diseases like osteogenesis imperfecta. The hydroxylation of proline residues by prolyl 4-hydroxylase is essential for collagen formation. Hyp (hydroxyproline) stabilizes the triple helix through stereoelectronic effects, while substitutions like fluoroproline can also influence stability. The structure of collagen fibrils is hierarchical, with microfibrils assembling into larger fibrils. The mechanical properties of collagen fibrils, including their strength and elasticity, are influenced by factors such as cross-linking and hydration. Synthetic collagen-like materials have been developed using chemical synthesis and self-assembly, offering potential applications in biomaterials and nanotechnology. The study of collagen structure and stability continues to provide insights into its biological functions and potential uses in medicine and materials science.