Studies of chain substitution caused sub-fibril level differences in stiffness and ultrastructure of wildtype and oim/oim collagen fibers using multifrequency-AFM and molecular modeling.

نویسندگان

  • Tao Li
  • Shu-Wei Chang
  • Naiara Rodriguez-Florez
  • Markus J Buehler
  • Sandra Shefelbine
  • Ming Dao
  • Kaiyang Zeng
چکیده

Molecular alteration in type I collagen, i.e., substituting the α2 chain with α1 chain in tropocollagen molecule, can cause osteogenesis imperfecta (OI), a brittle bone disease, which can be represented by a mouse model (oim/oim). In this work, we use dual-frequency Atomic Force Microscopy (AFM) and incorporated with molecular modeling to quantify the ultrastructure and stiffness of the individual native collagen fibers from wildtype (+/+) and oim/oim diseased mice humeri. Our work presents direct experimental evidences that the +/+ fibers have highly organized and compact ultrastructure and corresponding ordered stiffness distribution. In contrast, oim/oim fibers have ordered but loosely packed ultrastructure with uncorrelated stiffness distribution, as well as local defects. The molecular model also demonstrates the structural and molecular packing differences between +/+ and oim/oim collagens. The molecular mutation significantly altered sub-fibril structure and mechanical property of collagen fibers. This study can give the new insight for the mechanisms and treatment of the brittle bone disease.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Structure–mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model

The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tiss...

متن کامل

Multi-scale analysis of bone chemistry, morphology and mechanics in the oim model of osteogenesis imperfecta.

Osteogenesis imperfecta is a congenital disease commonly characterized by brittle bones and caused by mutations in the genes encoding Type I collagen, the single most abundant protein produced by the body. The oim model has a natural collagen mutation, converting its heterotrimeric structure (two α1 and one α2 chains) into α1 homotrimers. This mutation in collagen may impact formation of the mi...

متن کامل

This is a repository copy of Electron Microscopy Reveals Structural and Chemical Changes at the Nanometer Scale in the Osteogenesis Imperfecta Murine Pathology

Alternations of collagen and mineral at the molecular level may have a significant impact on the strength and toughness of bone. In this study, scanning transmission electron microscopy (STEM) and electron energy-loss spectroscopy (EELS) were employed to study structural and compositional changes in bone pathology at nanometer spatial resolution. Tail tendon and femoral bone of osteogenesis imp...

متن کامل

Structural and mechanical differences between collagen homo- and heterotrimers: relevance for the molecular origin of brittle bone disease.

Collagen constitutes one-third of the human proteome, providing mechanical stability, elasticity, and strength to organisms. Normal type I collagen is a heterotrimer triple-helical molecule consisting of two α-1 chains and one α-2 chain. The homotrimeric isoform of type I collagen, which consists of three α-1 chains, is only found in fetal tissues, fibrosis, and cancer in humans. A mouse model ...

متن کامل

Myocardial mechanics and collagen structure in the osteogenesis imperfecta murine (oim).

Because the amount and structure of type I collagen are thought to affect the mechanics of ventricular myocardium, we investigated myocardial collagen structure and passive mechanical function in the osteogenesis imperfecta murine (oim) model of pro-alpha2(I) collagen deficiency, previously shown to have less collagen and impaired biomechanics in tendon and bone. Compared with wild-type litterm...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Biomaterials

دوره 107  شماره 

صفحات  -

تاریخ انتشار 2016