AFM indentation of aorta and lung reveals tissue-specific micromechanical degradation with age in a mouse model of severe Marfan syndrome

Marfan syndrome (MFS) is an autosomal dominant disease that causes connective tissue disorders due to mutation of the fibrillin-1 gene, FBN1. This study aimed to characterize the microelastic properties of aorta and lung tissues from wild type (WT) and age-matched FBN1-underexpressing mutant (MT) mice to identify tissue-specific biomechanical effects of aging and cardiopulmonary disease in MFS. Atomic force microscopy (AFM) was used to indent intact lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition (HED) analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between MT and WT tissues. By contrast, the media layer of MT aorta showed progressive structural and mechanical degradation, with a modulus 50% softer than aged-matched WT media by 3.5 months old. MT lung also revealed rapid mechanical deterioration during adulthood, and was 90% softer than WT lung at 3.5 months. The findings reveal micromechanical softening of elastin-rich aorta and lung tissues in aging MT mice, providing insights into the biomechanical consequences of MFS.