Strain-induced collagen denaturation is rate dependent in failure of cerebral arteries

Anderl, William J.; Pearson, Noah; Converse, Matthew I.; Yu, S. Michael; Monson, Kenneth L.

doi:10.1016/j.actbio.2023.04.032

Cited by 2 publications

(1 citation statement)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our lab also demonstrated that CHPs have high serum stability, which allows sustained collagen binding under in vivo conditions . We demonstrated that the CHPs can be used to detect bone remodeling activity during development and disease progression, ,− mechanical damage to collagen in tendons, ,− invasive cancer, fibrosis, and other pathologies − (Figure B). Due to their simple chemical structure, the CHPs can even be conjugated to either small molecules or macromolecules for localizing therapeutics to inflamed tissues (Figure B). − These striking properties of CHPs are made possible by two key aspects of the CHPs.…”

Section: From Collagen Mimetics To Collagen Hybridizationmentioning

confidence: 72%

From Collagen Mimetics to Collagen Hybridization and Back

Ratnatilaka Na Bhuket,

Li,

2024

Acc. Chem. Res.

Self Cite

View full text Add to dashboard Cite

Conspectus Facilitated by the unique triple-helical protein structure, fibrous collagens, the principal proteins in animals, demonstrate a dual function of serving as building blocks for tissue scaffolds and as a bioactive material capable of swift renewal in response to environmental changes. While studies of triple-helical collagen mimetic peptides (CMPs) have been instrumental in understanding the molecular forces responsible for the folding and assembly of triple helices, as well as identifying bioactive regions of fibrous collagen molecules, single-strand CMPs that can specifically target and hybridize to denatured collagens (i.e., collagen hybridizing peptides, CHPs) have proven useful in identifying the remodeling activity of collagen-rich tissues related to development, homeostasis, and pathology. Efforts to improve the utility of CHPs have resulted in the development of new skeletal structures, such as dimeric and cyclic CHPs, as well as the incorporation of artificial amino acids, including fluorinated proline and N-substituted glycines (peptoid residues). In particular, dimeric CHPs were used to capture collagen fragments from biological fluid for biomarker study, and the introduction of peptoid-based collagen mimetics has sparked renewed interest in peptidomimetic research because peptoids enable a stable triple-helical structure and the presentation of an extensive array of side chain structures offering a versatile platform for the development of new collagen mimetics. This Account will cover the evolution of our research from CMPs as biomaterials to ongoing efforts in developing triple-helical peptides with practical theranostic potential in targeting denatured and damaged collagens. Our early efforts in functionalizing natural collagen scaffolds via noncovalent modifications led to the discovery of an entirely new use of CMPs. This discovery resulted in the development of CHPs that are now used by many different laboratories for the investigation of pathologies associated with changes in the structures of extracellular matrices including fibrosis, cancer, and mechanical damage to collagen-rich, load-bearing tissues. Here, we delve into the essential design features of CHPs contributing to their collagen binding properties and practical usage and explore the necessity for further mechanistic understanding of not only the binding processes (e.g., binding domain and stoichiometry of the hybridized complex) but also the biology of collagen degradation, from proteolytic digestion of fibrils to cellular processing of collagen fragments. We also discuss the strengths and weaknesses of peptoid-based triple-helical peptides as applied to collagen hybridization touching on thermodynamic and kinetic aspects of triple-helical folding. Finally, we highlight current limitations and future directions in the use of peptoid building blocks to develop bioactive collagen mimetics as new functional biomaterials.

show abstract

Section: From Collagen Mimetics To Collagen Hybridizationmentioning

confidence: 72%

From Collagen Mimetics to Collagen Hybridization and Back

Ratnatilaka Na Bhuket,

Li,

2024

Acc. Chem. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

Assessing microstructural damage in paediatric aortic coarctation tissue during benchtop balloon angioplasty and stenting

Linnane,

Johnston,

Kenny

et al. 2024

Preprint

View full text Add to dashboard Cite

Endovascular stenting of native aortic coarctation has become standard treatment for children and young adults due to the shorter hospital stay and recovery time, lower procedural risk and less invasive nature. However, despite these advantages, neonatal coarctation remains a surgically treated lesion, owing to the challenges of vessel growth and stent design. Plain old balloon angioplasty (POBA) of neonatal coarctation has been used as a treatment modality in the past but concern around vessel damage and aneurysm formation limited its widespread adoption. To-date, stenting has often been preferred over POBA treatment to minimise tissue damage but very little evidence has been gathered to establish the degree of tissue damage during intravascular procedures in neonatal coarctation tissue. The aim of this study was to perform balloon angioplasty and stenting on coarctation the aorta samples harvested at the time of surgery from neonatal patients and visualise the deformation under ultrasound guidance. From this, the novel collagen hybridizing peptide (CHP) was used to assess the level of collage denaturation and microstructural damage this tissue experienced when undergoing these procedures. The results demonstrate that balloon angioplasty singularly is not a viable treatment option at maintaining the lumen diameter unless higher levels of stretch are achieved to permanently deform the tissue. Five out of six neonatal coarctation samples were successfully stented with no stent failure, proving that stent insertion is a viable option to achieve the desired lumen diameter. In addition, for both procedures, increased collagen damage was observed with higher tissue strain. Overall, this work would suggest stent placement as the best option to achieve reliable lumen gain and to limit the level of the level of collagen damage when stretching the tissue to achieve the required lumen diameter.

show abstract

Strain-induced collagen denaturation is rate dependent in failure of cerebral arteries

Cited by 2 publications

References 52 publications

From Collagen Mimetics to Collagen Hybridization and Back

From Collagen Mimetics to Collagen Hybridization and Back

Assessing microstructural damage in paediatric aortic coarctation tissue during benchtop balloon angioplasty and stenting

Contact Info

Product

Resources

About