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:10437626
- 负责人:
- 金额:$ 35.54万
- 依托单位:
- 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 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AffinityAmino AcidsBindingBiomechanicsCartilageCartilage injuryClinicalCollagenCollagen FibrilDNADegenerative polyarthritisDense Connective TissueDetectionDevelopmentDiffusionDigestionDiseaseElementsEvolutionExhibitsExperimental ModelsFatigueFissuralFutureGoalsHybridsIn SituInflammatory ResponseInjuryKineticsLabelLigamentsMechanical StressMechanicsMethodsMolecularMolecular ProbesMolecular TargetMusculoskeletalMusculoskeletal DiseasesNatureOutcomes ResearchPainPenetrationPeptide HydrolasesPeptidesPredispositionProcessProtocols documentationReactionReportingResearchRotator CuffSensitivity and SpecificitySpecimenStainsStressStructureTechniquesTechnologyTendinopathyTendon structureTimeTissuesTrypsinWeight-Bearing stateWorkarticular cartilagebasecarboxyfluoresceincell injuryclinically relevantclinically significantdetection methoddisabilityenthalpyexperimental studyfluorophoreimprovedin vivo monitoringinsightmacrophagemechanical loadmechanical propertiesmeltingmusculoskeletal injurynext generationnovelnovel diagnosticsnovel therapeuticsresponsesoft tissuesynthetic peptidetargeted deliverytargeted 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
使用胶原杂交肽检测胶原机械损伤。
承重组织的机械性损伤导致许多临床上显著的病症(例如,肌腱病、旋转器
但我们对机械损伤组织的损伤过程了解有限,
应力这项研究的总体目标是对负荷的生物力学有新的认识
通过将胶原杂交肽(CHP)技术发展成为一种新的
机械损伤检测方法据报道,CHP结合变性胶原蛋白链,
通过蛋白酶活性或通过机械损伤,以类似于引物结合到熔化的DNA的方式,
PCR法我们建议通过开发新的CHP来大大扩展CHP损坏检测的能力
其较小,以便更快地扩散到致密的肌肉骨骼组织中,并表现出加速的结合动力学,
更快地报告损坏情况。我们还将开发一种新的CHP,仅在与胶原蛋白结合时才会发出荧光,
消除了对染色和清洗组织的需要,并使CHP能够在过载时用作损伤测量仪,
组织中然后,我们将为现有和新的CHP的使用开发优化的协议,确定
肌肉骨骼软组织中胶原纤维应变与CHP结合之间的关系,并定量
将CHP定位与其他技术进行比较。最后,我们将应用CHP靶向来阐明这种关系
组织水平的机械负荷和分子水平上对胶原的机械损伤之间的关系。我们将
重点关注两个重要的肌肉骨骼组织的相当大的临床相关性:肌腱和关节
软骨考虑到胶原蛋白损伤在肌肉骨骼损伤和疾病中的广泛影响,
深入了解分子水平胶原蛋白损伤与机械过载之间的关系
将为承重组织的生物力学提供新的见解,并有助于开发新的诊断方法。
以及用于管理肌肉骨骼疾病的疗法。
项目成果
期刊论文数量(12)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Collagen fibrils from both positional and energy-storing tendons exhibit increased amounts of denatured collagen when stretched beyond the yield point.
当拉伸超过屈服点时,来自位置肌腱和储能肌腱的胶原原纤维表现出变性胶原蛋白的数量增加。
- DOI:10.1016/j.actbio.2022.11.018
- 发表时间:2023
- 期刊:
- 影响因子:9.7
- 作者:Lin,AllenH;Slater,ChristopherA;Martinez,Callie-Jo;Eppell,StevenJ;Yu,SMichael;Weiss,JeffreyA
- 通讯作者:Weiss,JeffreyA
Peptoid Residues Make Diverse, Hyperstable Collagen Triple-Helices.
- DOI:10.1021/jacs.1c00708
- 发表时间:2021-07-28
- 期刊:
- 影响因子:15
- 作者:Kessler, Julian L.;Kang, Grace;Qin, Zhao;Kang, Helen;Whitby, Frank G.;Cheatham, Thomas E., III;Hill, Christopher P.;Li, Yang;Yu, S. Michael
- 通讯作者:Yu, S. Michael
Load transfer, damage, and failure in ligaments and tendons.
- DOI:10.1002/jor.24134
- 发表时间:2018-12
- 期刊:
- 影响因子:0
- 作者:Zitnay JL;Weiss JA
- 通讯作者:Weiss JA
Collagen denaturation is initiated upon tissue yield in both positional and energy-storing tendons.
- DOI:10.1016/j.actbio.2020.09.056
- 发表时间:2020-12
- 期刊:
- 影响因子:9.7
- 作者:Lin AH;Allan AN;Zitnay JL;Kessler JL;Yu SM;Weiss JA
- 通讯作者:Weiss JA
Tendons exhibit greater resistance to tissue and molecular-level damage with increasing strain rate during cyclic fatigue.
- DOI:10.1016/j.actbio.2021.07.045
- 发表时间:2021-10-15
- 期刊:
- 影响因子:9.7
- 作者:Zitnay JL;Lin AH;Weiss JA
- 通讯作者:Weiss JA
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JEFFREY A. WEISS其他文献
JEFFREY A. WEISS的其他文献
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{{ truncateString('JEFFREY A. WEISS', 18)}}的其他基金
Lab-to-User Training and Dissemination for the FEBio Software Suite
FEBio 软件套件的实验室对用户培训和传播
- 批准号:
10189583 - 财政年份:2019
- 资助金额:
$ 35.54万 - 项目类别:
Lab-to-User Training and Dissemination for the FEBio Software Suite
FEBio 软件套件的实验室对用户培训和传播
- 批准号:
10401860 - 财政年份:2019
- 资助金额:
$ 35.54万 - 项目类别:
Lab-to-User Training and Dissemination for the FEBio Software Suite
FEBio 软件套件的实验室对用户培训和传播
- 批准号:
10019547 - 财政年份:2019
- 资助金额:
$ 35.54万 - 项目类别:
Lab-to-User Training and Dissemination for the FEBio Software Suite
FEBio 软件套件的实验室对用户培训和传播
- 批准号:
10670059 - 财政年份:2019
- 资助金额:
$ 35.54万 - 项目类别:
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
- 批准号:
9926821 - 财政年份:2018
- 资助金额:
$ 35.54万 - 项目类别:
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
- 批准号:
10158440 - 财政年份:2018
- 资助金额:
$ 35.54万 - 项目类别:
Computational Framework for Multiscale Mechanics of Connective Tissues
结缔组织多尺度力学计算框架
- 批准号:
8439979 - 财政年份:2012
- 资助金额:
$ 35.54万 - 项目类别:
Computational Framework for Multiscale Mechanics of Connective Tissues
结缔组织多尺度力学计算框架
- 批准号:
8554764 - 财政年份:2012
- 资助金额:
$ 35.54万 - 项目类别:
Computational Framework for Multiscale Mechanics of Connective Tissues
结缔组织多尺度力学计算框架
- 批准号:
8727295 - 财政年份:2012
- 资助金额:
$ 35.54万 - 项目类别:
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