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Abstract We examined the mechanical deformation of valve interstitial cells (VICs) in the anterior leaflet of the tricuspid valve and explored the relationship between the extracellular matrix (ECM) structure and cellular mechanics. Fresh porcine hearts were used to prepare specimens, subjected to biaxial tensile testing, and imaged using confocal microscopy with VIC nuclei staining. A multi-scale computational framework was developed to analyze cellular deformation and orientation within the ECM, using nuclear aspect ratio (NAR) as a metric. Experimental results showed that NAR values increased with mechanical loading, from 2.57±0.72 in a traction-free state to 3.4±1.29 at 130 kPa. Model predictions aligned with experimental findings. They also highlighted the significant impact of ECM fiber orientation on VIC nuclei deformation. These results indicate that mechanical forces profoundly influence cellular morphology and, potentially, their function. Further development of models is necessary to understand the complex interplay between the mechanical environment and cellular responses, crucial for identifying how mechanical forces affect tricuspid valve function and malfunction. 

Elastin is present in the extracellular matrix (ECM) of connective tissues, and its mechanical properties are well documented. In Marfan syndrome, however, the inability to properly code for the protein fibrillin-1 prematurely leads to the degradation and loss of elastin fiber integrity in the ECM. In this study, the role of elastin in the ECM of the anterior leaflet of the tricuspid valve was investigated by examining the biomechanical behavior of porcine leaflets before and after the application of the enzyme elastase. Five loading protocols were applied to the leaflet specimens in two groups (elastase-treated and control samples). The mechanical response following elastase application yielded a significantly stiffer material in both the radial and circumferential directions. At a physiological level of stress (85 kPa), the elastase group had an average strain of 26.21% and 6.32% in the radial and circumferential directions, respectively, at baseline prior to elastase application. Following elastase treatment, the average strain was 5.28% and 0.97% in the radial and circumferential directions, respectively. No statistically significant change was found in the control group following sham treatment with phosphate-buffered saline (PBS). Two-photon microscopy images confirmed that after the removal of elastin, the collagen fibers displayed a loss of undulation. With a significant reduction in radial compliance, the ability to withstand physiological loads may be compromised. As such, an extracellular matrix that is structurally deficient in elastin may hinder normal tricuspid valve function.