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Targeting Collagen Mechanical Damage using Collagen Hybridizing Peptides

使用胶原蛋白杂交肽针对胶原蛋白机械损伤

基本信息

批准号：
10158440
负责人：
JEFFREY A. WEISS
金额：
$ 36.65万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-05 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10158440
关键词：
Affinity Amino Acids Binding Biomechanics Cartilage Cartilage injury Clinical Collagen Collagen Fibril DNA Degenerative polyarthritis Dense Connective Tissue Detection Development Diffusion Digestion Disease Elements Evolution Exhibits Experimental Models Fatigue Fissural Future Goals Hybrids In Situ Inflammatory Response Injury Kinetics Label Ligaments Mechanical Stress Mechanics Methods Molecular Molecular Probes Molecular Target Musculoskeletal Musculoskeletal Diseases Nature Outcomes Research Pain Penetration Peptide Hydrolases Peptides Predisposition Process Protocols documentation Reaction Reporting Research Rotator Cuff Sensitivity and Specificity Specimen Stains Stress Structure Techniques Technology Tendinopathy Tendon structure Time Tissues Trypsin Weight-Bearing state Work articular cartilage base carboxyfluorescein cell injury clinically relevant clinically significant detection method disability enthalpy experimental study fluorophore improved in vivo monitoring insight macrophage mechanical load mechanical properties melting musculoskeletal injury next generation novel novel diagnostics novel therapeutics response soft tissue synthetic peptide targeted delivery targeted treatment

项目摘要

SUMMARY Detection of Collagen Mechanical Damage using Collagen Hybridizing Peptides. Mechanical injury to load-bearing tissues leads to many clinically significant conditions (e.g. tendinosis, rotator cuff disease) but we have limited understanding of the injury process of tissues that are damaged by mechanical stress. The overall goal of the proposed research is to gain new understanding of the biomechanics of load bearing collagenous tissues by developing the collagen hybridizing peptide (CHP) technology into a new mechanical damage detection method. CHP has been reported to bind to denatured collagen strands originating from protease activity or by mechanical damage in a manner similar to primer binding to melted DNA during PCR. We propose to substantially expand the capabilities of CHP damage detection by developing new CHPs that are smaller for faster diffusion into dense musculoskeletal tissues and exhibit accelerated binding kinetics to allow faster damage reporting. We will also develop a new CHP that only fluoresces upon binding with collagen, eliminating the need to stain and wash tissues and enabling the CHP to serve as a damage gauge in overloaded tissues. We will then develop optimized protocols for the use of the existing and new CHPs, determine the relationship between collagen fibril strain and CHP binding in musculoskeletal soft tissues, and quantitatively compare CHP targeting to other techniques. Finally, we will apply CHP targeting to elucidate the relationship between tissue level mechanical loading and mechanical damage to collagen at the molecular level. We will focus on two important musculoskeletal tissues of considerable clinical relevance: tendons and articular cartilage. Considering the wide-spread impact of collagen damage in musculoskeletal injuries and diseases, in- depth understanding of the relationships between molecular level collagen damage and mechanical overloading will provide new insights into the biomechanics of load-bearing tissues as well as help develop new diagnostics and therapies for managing musculoskeletal disorders.

总结