skip to main content


Title: Anomalous mechanics of Zn 2+ -modified fibrin networks

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.

 
more » « less
Award ID(s):
1826623 2019745
NSF-PAR ID:
10216008
Author(s) / Creator(s):
; ; ; ;
Publisher / Repository:
Proceedings of the National Academy of Sciences
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
118
Issue:
10
ISSN:
0027-8424
Page Range / eLocation ID:
Article No. e2020541118
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    De novodesign provides an attractive approach, which allows one to test and refine the principles guiding metalloproteins in defining the geometry and reactivity of their metal ion cofactors. Although impressive progress has been made in designing proteins that bind transition metal ions including iron–sulfur clusters, the design of tetranuclear clusters with oxygen‐rich environments remains in its infancy. In previous work, we described the design of homotetrameric four‐helix bundles that bind tetra‐Zn2+clusters. The crystal structures of the helical proteins were in good agreement with the overall design, and the metal‐binding and conformational properties of the helical bundles in solution were consistent with the crystal structures. However, the correspondingapo‐proteins were not fully folded in solution. In this work, we design three peptides, based on the crystal structure of the original bundles. One of the peptides forms tetramers in aqueous solution in the absence of metal ions as assessed by CD and NMR. It also binds Zn2+in the intended stoichiometry. These studies strongly suggest that the desired structure has been achieved in theapostate, providing evidence that the peptide is able to actively impart the designed geometry to the metal cluster.

     
    more » « less
  2. Abstract

    Tailoring thermal transport by structural parameters could result in mechanically fragile and brittle networks. An indispensable goal is to design hierarchical architecture materials that combine thermal and mechanical properties in a continuous and cohesive network. A promising strategy to create such a hierarchical network targets additive manufacturing of hybrid porous voxels at nanoscale. Here we describe the convergence of agile additive manufacturing of porous hybrid voxels to tailor hierarchically and mechanically tunable objects. In one strategy, the uniformly distributed porous silica voxels, which form the basis for the control of thermal transport, are non-covalently interfaced with polymeric networks, yielding hierarchic super-elastic architectures with thermal insulation properties. Another additive strategy for achieving mechanical strength involves the versatile orthogonal surface hybridization of porous silica voxels retains its low thermal conductivity of 19.1 mW m−1 K−1, flexible compressive recovery strain (85%), and tailored mechanical strength from 71.6 kPa to 1.5 MPa. The printed lightweight high-fidelity objects promise thermal aging mitigation for lithium-ion batteries, providing a thermal management pathway using 3D printed silica objects.

     
    more » « less
  3. Fibrin is a naturally occurring protein network that forms a temporary structure to enable remodeling during wound healing. It is also a common tissue engineering scaffold because the structural properties can be controlled. However, to fully characterize the wound healing process and improve the design of regenerative scaffolds, understanding fibrin mechanics at multiple scales is necessary. Here, we present a strategy to quantify both the macroscale (1–10 mm) stress-strain response and the deformation of the mesoscale (10–1000 µm) network structure during unidirectional tensile tests. The experimental data were then used to inform a computational model to accurately capture the mechanical response of fibrin gels. Simultaneous mechanical testing and confocal microscopy imaging of fluorophore-conjugated fibrin gels revealed up to an 88% decrease in volume coupled with increase in volume fraction in deformed gels, and non-affine fiber alignment in the direction of deformation. Combination of the computational model with finite element analysis enabled us to predict the strain fields that were observed experimentally within heterogenous fibrin gels with spatial variations in material properties. These strategies can be expanded to characterize and predict the macroscale mechanics and mesoscale network organization of other heterogeneous biological tissues and matrices. 
    more » « less
  4. null (Ed.)
    Cells dynamically control their material properties through remodeling of the actin cytoskeleton, an assembly of cross-linked networks and bundles formed from the biopolymer actin. We recently found that cross-linked networks of actin filaments reconstituted in vitro can exhibit adaptive behavior and thus serve as a model system to understand the underlying mechanisms of mechanical adaptation of the cytoskeleton. In these networks, training, in the form of applied shear stress, can induce asymmetry in the nonlinear elasticity. Here, we explore control over this mechanical hysteresis by tuning the concentration and mechanical properties of cross-linking proteins in both experimental and simulated networks. We find that this effect depends on two conditions: the initial network must exhibit nonlinear strain stiffening, and filaments in the network must be able to reorient during training. Hysteresis depends strongly and non-monotonically on cross-linker concentration, with a peak at moderate concentrations. In contrast, at low concentrations, where the network does not strain stiffen, or at high concentrations, where filaments are less able to rearrange, there is little response to training. Additionally, we investigate the effect of changing cross-linker properties and find that longer or more flexible cross-linkers enhance hysteresis. Remarkably plotting hysteresis against alignment after training yields a single curve regardless of the physical properties or concentration of the cross-linkers. 
    more » « less
  5. Achieving a mesoporous structure in superinsulation materials is pivotal for guaranteeing a harmonious relationship between low thermal conductivity, high porosity, and low density. Herein, we report silica-based cryogel and aerogel materials by implementing freeze-drying and ambient-pressure-drying processes respectively. The obtained freeze-dried cryogels yield thermal conductivity of 23 mW m −1 K −1 , with specific surface area of 369.4 m 2 g −1 , and porosity of 96.7%, whereas ambient-pressure-dried aerogels exhibit thermal conductivity of 23.6 mW m −1 K −1 , specific surface area of 473.8 m 2 g −1 , and porosity of 97.4%. In addition, the fiber-reinforced nanocomposites obtained via freeze-drying feature a low thermal conductivity (28.0 mW m −1 K −1 ) and high mechanical properties (∼620 kPa maximum compressive stress and Young's modulus of 715 kPa), coupled with advanced flame-retardant capabilities, while the composite materials from the ambient pressure drying process have thermal conductivity of 28.8 mW m −1 K −1 , ∼200 kPa maximum compressive stress and Young's modulus of 612 kPa respectively. The aforementioned results highlight the capabilities of both drying processes for the development of thermal insulation materials for energy-efficient applications. 
    more » « less