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Microrheology encompasses a range of methods to measure the mechanical properties of soft materials. By characterizing the motion of embedded microscopic particles, microrheology extends the probing length scale and frequency range of conventional bulk rheology. Microrheology can be characterized into either passive or active methods based on the driving force exerted on probe particles. Tracer particles are driven by thermal energy in passive methods, applying minimal deformation to the assessed medium. In active techniques, particles are manipulated by an external force, most commonly produced through optical and magnetic fields. Small-scale rheology holds significant advantages over conventional bulk rheology, such as eliminating the need for large sample sizes, the ability to probe fragile materials non-destructively, and a wider probing frequency range. More importantly, some microrheological techniques can obtain spatiotemporal information of local microenvironments and accurately describe the heterogeneity of structurally complex fluids. Recently, there has been significant growth in using these minimally invasive techniques to investigate a wide range of biomedical systems both in vitro and in vivo . Here, we review the latest applications and advancements of microrheology in mammalian cells, tissues, and biofluids and discuss the current challenges and potential future advances on the horizon. 

Abstract The maintenance of hemostasis to ensure vascular integrity is dependent upon the rapid conversion of zymogen species of the coagulation cascade to their enzymatically active forms. This process culminates in the generation of the serine protease thrombin and polymerization of fibrin to prevent vascular leak at sites of endothelial cell injury or loss of cellular junctions. Thrombin generation can be initiated by the extrinsic pathway of coagulation through exposure of blood to tissue factor at sites of vascular damage, or alternatively by the coagulation factor (F) XII activated by foreign surfaces with negative charges, such as glass, through the contact activation pathway. Here, we used transient particle tracking microrheology to investigate the mechanical properties of fibrin in response to thrombin generation downstream of both coagulation pathways. We found that the structural heterogeneity of fibrin formation was dependent on the reaction kinetics of thrombin generation. Pharmacological inhibition of FXII activity prolonged the time to form fibrin and increased the degree of heterogeneity of fibrin, resulting in fibrin clots with reduced mechanical properties. Taken together, this study demonstrates a dependency of the physical biology of fibrin formation on activation of the contact pathway of coagulation. 

Abstract This investigation proposes a synthetic biofluid, artificial sputum medium (ASM) and xanthan gum (XG), that mimics the mucus from a patient with cystic fibrosis, and investigates the rheological properties both macroscopically and microscopically. Macroscopic rheological characterization cannot address the heterogeneity or the behavior of particle transport inside the mucus. Microscopic rheology enables the characterization of the microenvironment by using microparticles as probes. The addition of XG to ASM provides a tunable parameter that enables the mechanical properties to be consistent with real mucus. Particles that were suspended in a media of ASM with XG displayed a subdiffusive behavior at short timescales with a diffusive exponent that decreases with an increase in concentration of XG. At long timescales, particles that were suspended in ASM+XG with a concentration of XG of 0.1% to 0.4% displayed diffusive behavior. While in more concentrated samples (0.5% and 1.0%), the particles were constrained inside local elastic “cages”. The microscopic moduli that were calculated showed consistently lower moduli than rotational rheometry. This discrepancy suggests that the solutions of XG have a hierarchical structure that better represents the weakly associated microstructure of mucus that is found in real sputum.