Molecular-Level Collagen Damage is Strain Rate Dependent in Cerebral Arteries Stretched to Failure

Abstract

While soft tissues are commonly damaged during various mechanical loadings, the manifestation of this damage at the microstructural level is not fully understood. Specifically, while rate-induced stiffening has been previously observed in cerebral arteries, associated changes in microstructural damage patterns following gross tissue failure at high rates is largely not understood. In this study, we deformed porcine middle cerebral arteries to failure at 0.01 and >150 s-1 followed by probing for denatured tropocollagen using collagen hybridizing peptide (CHP). We found that collagen fibrils aligned with the loading direction experience less tropocollagen denaturation following high-rate failure than quasi-static failure. Furthermore, there was evidence of tropocollagen denaturation in fibrils transversely aligned to the loading axis at both rates, which, to our knowledge, is the first observation of collagen fibril damage due to transverse loading. These results indicate that strain rate is an important factor to consider when studying mechanically induced damage, and that fiber stretch may need to be reconsidered as a primary damage parameter in microstructurally informed continuum damage models due to the evidence of transverse damage.

Funding Information: The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), partially funded by the U.S. Army Medical Research and Development Command (Contract No. W81XWH-17-2-0008); National Science Foundation (NSF) (Award No. 2027367).

Declaration of Interests: The authors declare the following competing financial interest(s): Dr. S.M.Y. is a cofounder of 3Helix which commercializes the collagen hybridizing peptides. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethics Approval Statement: Göttingen minipigs were euthanized by Beuthanasia overdose following a protocol approved by the University of Utah Animal Care and Use Committee.

Keywords: collagen, Fibril, Molecular Damage, Soft Tissue Damage, viscoelasticity, Hyper-viscoelastic-damage, collagen hybridizing peptide, High Strain Rate, Cerebral Artery, traumatic brain injury