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1. Role of Microtubule Network in the Passive Anisotropic Viscoelasticity of Healthy Right Ventricle

   https://doi.org/10.1115/1.4064685  

   LeBar, Kristen ; Liu, Wenqiang ; Chicco, Adam J. ; Wang, Zhijie ( July 2024 , Journal of Biomechanical Engineering)

   Kristin S. Miller. (Ed.)

   Cardiomyocytes are viscoelastic and key determinants of right ventricle (RV) mechanics. Intracellularly, microtubules are found to impact the viscoelasticity of isolated cardiomyocytes or trabeculae; whether they contribute to the tissue-level viscoelasticity is unknown. Our goal was to reveal the role of the microtubule network in the passive anisotropic viscoelasticity of the healthy RV. Equibiaxial stress relaxation tests were conducted in healthy RV free wall (RVFW) under early (6%) and end (15%) diastolic strain levels, and at sub- and physiological stretch rates. The viscoelasticity was assessed at baseline and after the removal of microtubule network. Furthermore, a quasi-linear viscoelastic (QLV) model was applied to delineate the contribution of microtubules to the relaxation behavior of RVFW. After removing the microtubule network, RVFW elasticity and viscosity were reduced at the early diastolic strain level and in both directions. The reduction in elasticity was stronger in the longitudinal direction, whereas the degree of changes in viscosity were equivalent between directions. There was insignificant change in RVFW viscoelasticity at late diastolic strain level. Finally, the modeling showed that the tissue's relaxation strength was reduced by the removal of the microtubule network, but the change was present only at a later time scale. These new findings suggest a critical role of cytoskeleton filaments in RVFW passive mechanics in physiological conditions.

    

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2. Anomalous mechanics of Zn 2+ -modified fibrin networks

   https://doi.org/10.1073/pnas.2020541118  

   Xia, Jing ; Cai, Li-Heng ; Wu, Huayin ; MacKintosh, Frederick C. ; Weitz, David A. ( March 2021 , Proceedings of the National Academy of Sciences)

   Fibrin is the main component of blood clots. The mechanical properties of fibrin are therefore of critical importance in successful hemostasis. One of the divalent cations released by platelets during hemostasis is Zn²⁺; however, its effect on the network structure of fibrin gels and on the resultant mechanical properties remains poorly understood. Here, by combining mechanical measurements with three-dimensional confocal microscopy imaging, we show that Zn²⁺can tune the fibrin network structure and alter its mechanical properties. In the presence of Zn²⁺, fibrin protofibrils form large bundles that cause a coarsening of the fibrin network due to an increase in fiber diameter and reduction of the total fiber length. We further show that the protofibrils in these bundles are loosely coupled to one another, which results in a decrease of the elastic modulus with increasing Zn²⁺concentrations. We explore the elastic properties of these networks at both low and high stress: At low stress, the elasticity originates from pulling the thermal slack out of the network, and this is consistent with the thermal bending of the fibers. By contrast, at high stress, the elasticity exhibits a common master curve consistent with the stretching of individual protofibrils. These results show that the mechanics of a fibrin network are closely correlated with its microscopic structure and inform our understanding of the structure and physical mechanisms leading to defective or excessive clot stiffness.

    

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3. Mechanical behavior of nonwoven non-crosslinked fibrous mats with adhesion and friction

   https://doi.org/10.1039/c9sm00658c  

   Negi, V. ; Picu, R. C. ( July 2019 , Soft Matter)

   We present a study of the mechanical behavior of planar fibrous mats stabilized by inter-fiber adhesion. Fibers of various degrees of tortuosity and of infinite and finite length are considered in separate models. Fibers are randomly distributed, are not cross-linked, and interact through adhesion and friction. The variation of structural parameters such as the mat thickness and the mean segment length between contacts along given fibers with the strength of adhesion is determined. These systems are largely dissipative in that most of the work performed during deformation is dissipated frictionally and only a small fraction is stored as strain energy. The response of the mats to tensile loading has three regimes: a short elastic regime in which no sliding at contacts is observed, a well-defined sliding regime characterized by strain hardening, and a rapid stiffening regime at larger strains. The third regime is due to the formation of stress paths after the fiber tortuosity is pulled out and is absent in mats of finite length fibers. Networks of finite length fibers lose stability during the second regime of deformation. The scaling of the yield stress, which characterizes the transition between the first and the second regimes, and of the second regime's strain hardening modulus, with system parameters such as the strength of adhesion and friction and the degree of fiber tortuosity are determined. The strength of mats of finite length fibers is also determined as a function of network parameters. These results are expected to become useful in the design of electrospun mats and other planar fibrous non-cross-linked networks. 

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4. Sculpting Rupture‐Free Nuclear Shapes in Fibrous Environments

   https://doi.org/10.1002/advs.202203011  

   Jana, Aniket ; Tran, Avery ; Gill, Amritpal ; Kiepas, Alexander ; Kapania, Rakesh K. ; Konstantopoulos, Konstantinos ; Nain, Amrinder S. ( July 2022 , Advanced Science)

   Cytoskeleton‐mediated force transmission regulates nucleus morphology. How nuclei shaping occurs in fibrous in vivo environments remains poorly understood. Here suspended nanofiber networks of precisely tunable (nm–µm) diameters are used to quantify nucleus plasticity in fibrous environments mimicking the natural extracellular matrix. Contrary to the apical cap over the nucleus in cells on 2‐dimensional surfaces, the cytoskeleton of cells on fibers displays a uniform actin network caging the nucleus. The role of contractility‐driven caging in sculpting nuclear shapes is investigated as cells spread on aligned single fibers, doublets, and multiple fibers of varying diameters. Cell contractility increases with fiber diameter due to increased focal adhesion clustering and density of actin stress fibers, which correlates with increased mechanosensitive transcription factor Yes‐associated protein (YAP) translocation to the nucleus. Unexpectedly, large‐ and small‐diameter fiber combinations lead to teardrop‐shaped nuclei due to stress fiber anisotropy across the cell. As cells spread on fibers, diameter‐dependent nuclear envelope invaginations that run the nucleus's length are formed at fiber contact sites. The sharpest invaginations enriched with heterochromatin clustering and sites of DNA repair are insufficient to trigger nucleus rupture. Overall, the authors quantitate the previously unknown sculpting and adaptability of nuclei to fibrous environments with pathophysiological implications.

    

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5. Hyper-Viscoelastic 3D Response of Axons Subjected to Repeated Tensile Loads in Brain White Matter

   https://doi.org/10.1115/IMECE2022-97059  

   Agarwal, Mohit ; Pelegri, Assimina A. ( October 2022 , American Society of Mechanical Engineers)

   A novel finite element method (FEM) is developed to study mechanical response of axons embedded in extra cellular matrix (ECM) when subjected to harmonic uniaxial stretch under purely non-affine kinematic boundary conditions. The proposed modeling approach combines hyper-elastic (such as Ogden model) and time/frequency domain viscoelastic constitutive models to evaluate the effect of parametrically varying oligodendrocyte-axon tethering under harmonic stretch at 50Hz. A hybrid hyper-viscoelastic material (HVE) model enabled the analysis of repeated uniaxial load on stress propagation and damage accumulation in white matter.

   In the proposed FEM, oligodendrocyte connections to axons are depicted via a spring-dashpot model. This tethering technique facilitates contact definition at various locations, parameterizes connection points and varies stiffness of connection hubs. Results from a home-grown FE submodel configuration of a single oligodendrocyte tethered to axons at various locations are presented. Root mean square deviation (RMSD) are computed between stress-strain plots to depict trends in mechanical response. Steady-state dynamic (SSD) simulations show stress relaxation in axons. Gradual axonal softening under repetitive loads is illustrated employing Prony series - HVE models. Representative von-Mises stress plots indicate that undulated axons experience bending stresses along their tortuous path, suggesting greater susceptibility to damage accumulation and fatigue failure due to repeated strains.

    

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