期刊
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
卷 108, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jmbbm.2020.103835
关键词
Collagen steered molecular dynamics; Collagen nanomechanics; Cellular microenvironment; Collagen mechano-conformations; Tumor extravasation
资金
- Weill Cornell Graduate School of Medical Sciences (New York, NY, USA)
- Weill Medical College (New York, NY, USA) Clinical and Translational Science Center - National Center for Advancing Translational Sciences (NCATS) [UL1TR000457-06]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH, Bethesda, MD, USA) [R21AR051636, R01AR45748]
- Research Facilities Improvement Program from the National Center for Research Resources of the NIH [C06-RR1253801]
Structural proteins in the extracellular matrix are subjected to a range of mechanical loading conditions, including varied directions of force application. Molecular modeling suggests that these mechanical forces directly affect collagen's conformation and the subsequent mechanical response at the molecular level is complex. For example, tensile forces in the axial direction result in collagen triple helix elongation and unwinding, while perpendicular forces can cause local triple helix disruption. However, the effects of more complicated mechanical loading, such as the effect of axial pretension on collagen bending and triple helix microunfolding are unknown. In this study we used steered molecular dynamics to first model a collagen peptide under axial tension and then apply a perpendicular bending force. Axial tension causes molecular elongation and increased the subsequent perpendicular bending stiffness, but surprisingly did not increase the predicted collagen triple helix microunfolding threshold. We believe these results elucidate a key potential mechanism by which microscale mechanical loads translate from cellular and micro scales down to the nano and atomistic. Further, these data predict that cryptic force-induced collagen triple helix unwinding is axial-deformation independent, supporting the possibility that cell traction forces could be a key molecular mechanism to alter the cellular matrix microenvironment to facilitate collagen enzymatic degradation and subsequent cellular migration, such as in tumor extravasation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据