PhD Scientific Days 2022

Translational Medicine II. (Poster discussion will take place in the Aula during the Coffee Break)

Nanoscale features of Marfan and non-Marfan aorta-derived fibrillin-1 microfibrils

Text of the abstract

Introduction: Fibrillin microfibrils are essential structures of the extracellular matrix that play a fundamental role in multiple physiological functions of connective tissues. They are abundant in highly dynamic tissues, such as the aorta, where fibrillin-1 microfibrils are involved in vascular elasticity. Their biological relevance is reflected by the linkage of mutations in the fibrillin-1-encoding FBN1 gene to a group of connective tissue disorders known as fibrillinopathies, the most notable of which is Marfan syndrome, which is associated with skeletal, ocular and cardiovascular defects. Aortic involvement, in the form of aortic dilation, dissection, or rupture, represents the main cause of mortality among Marfan syndrome patients.
Aims: To assess and compare the structural and mechanical characteristics of fibrillin-1 microfibrils isolated from human Marfan and non-Marfan aortic tissue.
Method: Aortic wall samples were obtained from patients undergoing specific cardiovascular surgical interventions. The deposition of fibrillin-1 in the extracellular matrix was analyzed by using two-photon microscopy. Fibrillin-rich microfibrils were extracted by bacterial collagenase digestion and purified by size-exclusion chromatography. Atomic force microscopy was used to visualize and study the microfibrillar assemblies.
Results: In both groups, fibrillin-1 microfibrils of various lengths were observed, exhibiting the typical “beads-on-a-string” appearance. A mean periodicity of approximately 52 nm was recorded. Following initial measurements, no significant differences regarding nanostructural features were identified between the two groups.
Conclusion: We theorize that mutations in the FBN1 gene lead to nanomechanical variations in the Marfan fibrillin-1 microfibrils rather than morphological modifications. Further measurements are expected to reveal the microfibril-level characteristics that lead to the development symptoms involving the Marfan aorta.
Funding: This research was funded by a grant from the Hungarian National Research, Development and Innovation Office (K135360).