New Mechanical Markers for Tracking the Progression of Myocardial Infarction

Abstract

The mechanical properties of soft tissues can often be strongly correlated with the progression of various diseases, such as myocardial infarction (MI). However, the dynamic mechanical properties of cardiac tissues during MI progression remain poorly understood. Herein, we investigate the rheological responses of cardiac tissues at different stages of MI (i.e., earlystage, mid-stage, and late-stage) with atomic force microscopybased microrheology. Surprisingly, we discover that all cardiac tissues exhibit a universal two-stage power-law rheological behavior at different time scales. The experimentally found power-law exponents can capture an inconspicuous initial rheological change, making them particularly suitable as markers for early-stage MI diagnosis. We further develop a self-similar hierarchical model to characterize the progressive mechanical changes from subcellular to tissue scales. The theoretically calculated mechanical indexes are found to markedly vary among different stages of MI. These new mechanical markers are applicable for tracking the subtle changes of cardiac tissues during MI progression.

Viscoelastic Multiscale Mechanical Indexes for Assessing Liver Fibrosis and Treatment Outcomes

“…Our results have significant implications for the understanding of how dynamical mechanical properties alter with liver fibrosis and MSCs administration and further complement those of earlier studies of hepatic static mechanics. This study substantiates and extends upon the trends elucidated in our prior research, as we develop a new viscoelastic multiscale indexes-based mechanical criteria for assessing liver fibrosis and treatment outcomes. This multidimensional assessment approach can be potentially applied to other biological tissues, providing insight into complicated disease evolution, prognosis evaluation, and guiding the biomedical material design.…”

“…Based on the hierarchical structures of biological tissues, we have previously developed a self-similar mechanical model, as illustrated in Figure A. Using this theoretical framework, we can perfectly capture the dynamical mechanical characteristics of all liver tissues, as shown in Figure B.…”

“…Although the static mechanical information on livers has been gradually studied, there is still limited knowledge regarding how their dynamic mechanical properties (e.g., viscoelasticity) associate with liver fibrosis progression and antifibrosis therapy. ,, Despite certain approaches, such as shear wave elastography and magnetic resonance elastography, having been developed to measure the storage and loss moduli of livers, they suffer from significant limitations, including high variability, low accuracy, and inability to quantitatively reflect the dynamic processes of fibrogenesis and treatment. It is now well established from a variety of studies that atomic force microscopy (AFM) proved an important technique to disclose the viscoelastic properties of individual cells , and soft tissues ,− at micro- and nanoscales, especially for those with various disorders, such as cardiovascular diseases, osteoarthritis, and cancers. ,, To date, however, there remains a paucity of robust mechanical markers that can accurately capture the fibrosis progression and evaluate the therapeutic outcomes.…”

“…To circumvent the challenges of in-depth understanding of dynamic mechanics of soft tissues, we recently developed an AFM-based microrheology to examine the viscoelastic properties of cardiac tissues during the progression of myocardial infarction . Here, we extend this methodology to investigate the creep responses of livers with varying statuses (healthy, fibrotic, and MSCs-treated fibrotic).…”

“…Currently, it remains a significant challenge to characterize the dynamical mechanical changes of fibrotic livers, despite the interaction between alterations in static tissue mechanics and disease progression having been established. , By using the AFM-based microrheology approach (Figures S1 and S2), we investigated the dynamical creep responses of different livers, as summarized in Figures A,B and Table S1. The time-dependent creep compliance J ( t ) is defined as the ratio of strain ε­( t ) to applied mechanical stress σ­( t ).…”