Viscoelastic Multiscale Mechanical Indexes for Assessing Liver Fibrosis and Treatment Outcomes

Abstract

Understanding liver tissue mechanics, particularly in the context of liver pathologies like fibrosis, cirrhosis, and carcinoma, holds pivotal significance for assessing disease severity and prognosis. Although the static mechanical properties of livers have been gradually studied, the intricacies of their dynamic mechanics remain enigmatic. Here, we characterize the dynamic creep responses of healthy, fibrotic, and mesenchymal stem cells (MSCs)-treated fibrotic lives. Strikingly, we unearth a ubiquitous two-stage power-law rheology of livers across different time scales with the exponents and their distribution profiles highly correlated to liver status. Moreover, our self-similar hierarchical theory effectively captures the delicate changes in the dynamical mechanics of livers. Notably, the viscoelastic multiscale mechanical indexes (i.e., power-law exponents and elastic stiffnesses of different hierarchies) and their distribution characteristics prominently vary with liver fibrosis and MSCs therapy. This study unveils the viscoelastic characteristics of livers and underscores the potential of proposed mechanical criteria for assessing disease evolution and prognosis.

Enhancing liver fibrosis diagnosis and treatment assessment: a novel biomechanical markers-based machine learning approach

“…This difficulty can lead to an incorrect calculation of the overall sample deformation during the creep response, resulting in invalid theoretical calculations; (2) the creep response can be significantly influenced by the localized tissue microstructure, which exhibits notable variability at the microscale. Our previous histological analysis (Chang et al 2023b) revealed a noticeable heterogeneity in tissue components. The presence of excessive porous tissue microstructure can further contribute to an unstable creep response during force clamping, leading to difficulties in theoretical analyses.…”

“…The research process was built upon the dataset initially compiled and analyzed in our prior research (Chang et al 2023b). In our previous study, we extensively characterized the dynamic creep responses and multiscale viscoelastic properties of healthy, fibrotic, and treated liver tissues, employing AFM-microrheology and self-similar hierarchical theory (figure 1(A)).…”

“…In our previous studies, we developed a set of multiscale biomechanical markers using atomic force microscopy (AFM) -based microrheology (Chang et al 2023a) and the self-similar hierarchical model (Hang et al 2021(Hang et al , 2022 to accurately characterize the viscoelastic and nonlinear mechanical properties of liver tissues. These indexes have shown remarkable potential in detecting nuanced viscoelastic changes in liver fibrosis and post-MSCs treatment scenarios (Chang et al 2023b). Despite their significant insights into the dynamic mechanical alterations in various liver conditions, these mechanical markers still lack comprehensive validation and clinical implementation.…”

Measuring the viscoelastic relaxation function of cells with a time-dependent interpretation of the Hertz-Sneddon indentation model

“…For instance, a large volume of AFM studies reported that individual cancer cells are less rigid than their normal counterparts [3] , [9] , [10] , [11] , [12] , and the same trend was also observed comparing normal and cancerous tissues of the human breast [13] . Beyond cancer, other diseases like osteoarthritis [14] , [15] , tissue fibrosis [16] , [17] and myocardial infarction [18] exhibit distinguished mechanical signatures, which can be used as an advantageous technique to develop early diagnosis methods. More recently, a few works reported the strong role the microenvironment topography plays in cell mechanics.…”

Emergence, Pattern, and Frequency of Spontaneous Waves in Spreading Epithelial Monolayers

“…Collective cell migration is essential for many physiological and pathological processes, including embryogenesis, tissue development, wound healing, and cancer metastasis. − Much effort has been devoted to comprehensively exploring the intricate physical mechanisms that underlie collective motion behaviors. − Recent experiments have uncovered a striking emergent phenomenon, wherein a mechanical wave spontaneously arises and propagates within collective cells, which was widely observed in confined clusters, expanding colonies and colliding monolayers . Especially, Madin–Darby Canine Kidney (MDCK) epithelial cells exhibit an X-pattern mechanical wave during their expansion toward free regions .…”