Real- time single- molecule observation of incipient collagen fibrillogenesis and remodeling

• 成果类型: Article
• 署名作者: Roth, Jonathan; Hoop, Cody; Williams, Jonathan K.; Nanda, Vikas; Baum, Jean
• 署名单位: Rutgers University System; Rutgers University New Brunswick; Rutgers University System; Rutgers University New Brunswick; Rutgers University Biomedical & Health Sciences; Rutgers University System; Rutgers University New Brunswick; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); Bristol-Myers Squibb
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11844
• DOI: 10.1073/pnas.2401133121
• 发表日期: 2024-08-13
• 关键词: i collagen; fibrils; ORGANIZATION; microscopy; GROWTH

摘要

The hierarchic assembly of fibrillar collagen into an extensive and ordered supramolecular protein fibril is critical for extracellular matrix function and tissue mechanics. Despite decades of study, we still know very little about the complex process of fibrillogenesis, particularly at the earliest stages where observation of rapidly forming, nanoscale intermediates challenges the spatial and temporal resolution of most existing microscan observe details of the first few minutes of collagen fibril formation and growth on a mica surface in solution. A defining feature of fibrillar collagens is a 67- nm periodic banding along the fibril driven by the organized assembly of individual monomers over of small fibrils from an initial uniform height to structures that display the canonical banding within seconds. Fibrils grow in a primarily unidirectional manner, with frayed ends of the growing tip latching onto adjacent fibrils. We find that, even at extremely early time points, remodeling of growing fibrils proceeds through bird- caging intermediates and propose that these dynamics may provide a pathway to mature hierarchic and pathways for remodeling of the supramolecular assembly of collagen during the inception of fibrillogenesis.