Fibrin fiber deformation mechanisms: insights from phenomenological modeling to molecular details

摘要

Abstract The deformation mechanism of fibrin fibers has been a long-standing challenge to uncover due to the fiber’s complex structure and mechanical behaviors. In this paper, a phenomenological, bilinear, force-strain model is derived to accurately reproduce the fibrin fiber force-strain curve, and then, the phenomenological model is converted to a mechanistic model using empirical relationships developed from particle simulation data. The mechanistic model assumes that the initial linear fibrin fiber force-strain response is due to entropic extension of polypeptide chains, and the final linear response is due to enthalpic extension of protofibrils. This model is the first fibrin fiber tensile force-strain equation to simultaneously (1) reproduce the bilinear force-strain curve of fibrin fibers in tension; (2) explicitly include the number of protofibrils through the fibrin fiber cross section, persistence length of αCdocumentclass[12pt]{minimal} usepackage{amsmath} usepackage{wasysym} usepackage{amsfonts} usepackage{amssymb} usepackage{amsbsy} usepackage{mathrsfs} usepackage{upgreek} setlength{oddsidemargin}{-69pt} begin{document}$$mathrm{alpha C}$$end{document}-regions, and stiffness of fibrin protofibrils; and (3) make demonstrably reasonable/accurate predictions of fibrin fiber mechanics when tempered against experimental results. The model predicted that the count of protofibrils through the cross section for the analyzed fibrin fibers is between 207 and 421, the persistence length of αCdocumentclass[12pt]{minimal} usepackage{amsmath} usepackage{wasysym} usepackage{amsfonts} usepackage{amssymb} usepackage{amsbsy} usepackage{mathrsfs} usepackage{upgreek} setlength{oddsidemargin}{-69pt} begin{document}$$alpha C$$end{document}-regions is ∼0.36nmdocumentclass[12pt]{minimal} usepackage{amsmath} usepackage{wasysym} usepackage{amsfonts} usepackage{amssymb} usepackage{amsbsy} usepackage{mathrsfs} usepackage{upgreek} setlength{oddsidemargin}{-69pt} begin{document}$$sim 0.36 mathrm{nm}$$end{document}, and the stiffness of protofibrils in a deforming fiber is ∼1.34nN/straindocumentclass[12pt]{minimal} usepackage{amsmath} usepackage{wasysym} usepackage{amsfonts} usepackage{amssymb} usepackage{amsbsy} usepackage{mathrsfs} usepackage{upgreek} setlength{oddsidemargin}{-69pt} begin{document}$$sim 1.34 nN/mathrm{strain}$$end{document}. The predicted αCdocumentclass[12pt]{minimal} usepackage{amsmath} usepackage{wasysym} usepackage{amsfonts} usepackage{amssymb} usepackage{amsbsy} usepackage{mathrsfs} usepackage{upgreek} setlength{oddsidemargin}{-69pt} begin{document}$$alpha C$$end{document}-region persistence length is within the range typical of amino acid residue lengths 0.34-0.4nm,documentclass[12pt]{minimal} usepackage{amsmath} usepackage{wasysym} usepackage{amsfonts} usepackage{amssymb} usepackage{amsbsy} usepackage{mathrsfs} usepackage{upgreek} setlength{oddsidemargin}{-69pt} begin{document}$$0.34-0.4 mathrm{nm},$$end{document} and the predicted protofibril stiffness is shown to correspond to half-staggered protofibrils of unfolded fibrin monomers. Our analysis supports the proposition that entropic extension of αCdocumentclass[12pt]{minimal} usepackage{amsmath} usepackage{wasysym} usepackage{amsfonts} usepackage{amssymb} usepackage{amsbsy} usepackage{mathrsfs} usepackage{upgreek} setlength{oddsidemargin}{-69pt} begin{document}$$alpha C$$end{document}-regions could be responsible for fibrin fiber’s initial force-strain stiffness and suggests a structural change in fibrin protofibrils during fibrin fiber deformation. The results from the model are compared to those from five candidate deformation mechanisms reported in the literature. Our work provides (1) strong quantitative support to a deformation mechanism that was previously supported by anecdote and qualitative argument, and (2) a model for rigorously analyzing fibrin fiber force-strain