Search for: All records

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. 

Tissues grow and remodel in response to mechanical cues, extracellular and intracellular signals experienced through various biological events, from the developing embryo to disease and aging. The macroscale response of soft tissues is typically nonlinear, viscoelastic anisotropic, and often emerges from the hierarchical structure of tissues, primarily their biopolymer fiber networks at the microscale. The adaptation to mechanical cues is likewise a multiscale phenomenon. Cell mechanobiology, the ability of cells to transform mechanical inputs into chemical signaling inside the cell, and subsequent regulation of cellular behavior through intra- and inter-cellular signaling networks, is the key coupling at the microscale between the mechanical cues and the mechanical adaptation seen macroscopically. To fully understand mechanics of tissues in growth and remodeling as observed at the tissue level, multiscale models of tissue mechanobiology are essential. In this review, we summarize the state-of-the art modeling tools of soft tissues at both scales, the tissue level response, and the cell scale mechanobiology models. To help the interested reader become more familiar with these modeling frameworks, we also show representative examples. Our aim here is to bring together scientists from different disciplines and enable the future leap in multiscale modeling of tissue mechanobiology. 

Extensive literature exists studying decentralized coordination and consensus, with considerable attention devoted to ensuring robustness to faults and attacks. However, most of the latter literature assumes that non-malicious agents follow simple stylized rules. In reality, decentralized protocols often involve humans, and understanding how people coordinate in adversarial settings is an open problem. We initiate a study of this problem, starting with a human subjects investigation of human coordination on networks in the presence of adversarial agents, and subsequently using the resulting data to bootstrap the development of a credible agent-based model of adversarial decentralized coordination. In human subjects experiments, we observe that while adversarial nodes can successfully prevent consensus, the ability to communicate can significantly improve robustness, with the impact particularly significant in scale-free networks. On the other hand, and contrary to typical stylized models of behavior, we show that the existence of trusted nodes has limited utility. Next, we use the data collected in human subject experiments to develop a data-driven agent-based model of adversarial coordination. We show that this model successfully reproduces observed behavior in experiments, is robust to small errors in individual agent models, and illustrate its utility by using it to explore the impact of optimizing network location of trusted and adversarial nodes.