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The extracellular matrix (ECM) is a dynamic and complex microenvironment that modulates cell behavior and cell fate. Changes in ECM composition and architecture have been correlated with development, differentiation, and disease progression in various pathologies, including breast cancer [1]. Studies have shown that aligned fibers drive a pro-metastatic microenvironment, promoting the transformation of mammary epithelial cells into invasive ductal carcinomaviathe epithelial-to-mesenchymal transition (EMT) [2]. The impact of ECM orientation on breast cancer metabolism, however, is largely unknown. Here, we employ two non-invasive imaging techniques, fluorescence-lifetime imaging microscopy (FLIM) and intensity-based multiphoton microscopy, to assess the metabolic states of cancer cells cultured on ECM-mimicking nanofibers in a random and aligned orientation. By tracking the changes in the intrinsic fluorescence of nicotinamide adenine dinucleotide and flavin adenine dinucleotide, as well as expression levels of metastatic markers, we reveal how ECM fiber orientation alters cancer metabolism and EMT progression. Our study indicates that aligned cellular microenvironments play a key role in promoting metastatic phenotypes of breast cancer as evidenced by a more glycolytic metabolic signature on nanofiber scaffolds of aligned orientation compared to scaffolds of random orientation. This finding is particularly relevant for subsets of breast cancer marked by high levels of collagen remodeling (e.g. pregnancy associated breast cancer), and may serve as a platform for predicting clinical outcomes within these subsets [3–6]. 

Thromboembolism – that is, clot formation and the subsequent fragmentation of clot – is a leading cause of death worldwide. Clots’ mechanical properties are critical determinants of both the embolization process and the pathophysiological consequences thereof. Thus, understanding and quantifying the mechanical properties of clots is important to our ability to treat and prevent thromboembolic disease. However, assessing these properties from in vivo clots is experimentally challenging. Therefore, we and others have turned to studying in vitro clot mimics instead. Unfortunately, there are significant discrepancies in the reported properties of these clot mimics, which have been hypothesized to arise from differences in experimental techniques and blood sources. The goal of our current work is therefore to compare the mechanical behavior of clots made from the two most common sources, human and bovine blood, using the same experimental techniques. To this end, we tested clots under pure shear with and without initial cracks, under cyclic loading, and under stress relaxation. Based on these data, we computed and compared stiffness, strength, work-to-rupture, fracture toughness, relaxation time constants, and prestrain. While clots from both sources behaved qualitatively similarly, they differed quantitatively in almost every metric. We also correlated each mechanical metric to measures of blood composition. Thereby, we traced this inter-species variability in clot mechanics back to significant differences in hematocrit, but not platelet count. Thus, our work suggests that the results of past studies that have used bovine blood to make in vitro mimics – without adjusting blood composition – should be interpreted carefully. Future studies about the mechanical properties of blood clots should focus on human blood alone. 

Constitutive models are important to biomechanics for two key reasons. First, constitutive modelling is an essential component of characterizing tissues’ mechanical properties for informing theoretical and computational models of biomechanical systems. Second, constitutive models can be used as a theoretical framework for extracting and comparing key quantities of interest from material characterization experiments. Over the past five decades, the Ogden model has emerged as a popular constitutive model in soft tissue biomechanics with relevance to both informing theoretical and computational models and to comparing material characterization experiments. The goal of this short review is threefold. First, we will discuss the broad relevance of the Ogden model to soft tissue biomechanics and the general characteristics of soft tissues that are suitable for approximating with the Ogden model. Second, we will highlight exemplary uses of the Ogden model in brain tissue, blood clot and other tissues. Finally, we offer a tutorial on fitting the one-term Ogden model to pure shear experimental data via both an analytical approximation of homogeneous deformation and a finite-element model of the tissue domain. Overall, we anticipate that this short review will serve as a practical introduction to the use of the Ogden model in biomechanics. This article is part of the theme issue ‘The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity’. 

When a thrombus breaks off and embolizes it can occlude vital vessels such as those of the heart, lung, or brain. These thromboembolic conditions are responsible for 1 in 4 deaths worldwide. Thrombus resistance to embolization is driven by its intrinsic fracture toughness as well as other, non-surface-creating dissipative mechanisms. In our current work, we identify and quantify these latter mechanisms toward future studies that aim to delineate fracture from other forms of dissipation. To this end, we use an in vitro thrombus mimic system to produce whole blood clots and explore their dissipative mechanics under simple uniaxial extension, cyclic loading, and stress-relaxation. We found that whole blood clots exhibit Mullins-like effect, hysteresis, permanent set, strain-rate dependence, and nonlinear stress-relaxation. Interestingly, we found that performing these tests under dry or submerged conditions did not change our results. However, performing these tests under room temperature or body temperature conditions yielded differences. Importantly, because we use venous blood our work is most closely related to venous in vivo blood clots. Overall, we have demonstrated that whole blood clots show several dissipative phenomena – similarly to hydrogels – that will be critical to our understanding of thrombus embolization.