PhD Scientific Days 2025

Poster Session II. - U: Cardiovascular Medicine and Research

Nanomechanical properties of fibrillin-1 microfibrils in normal and Marfan syndrome human aortic tissue

Name of the presenter

Șulea Cristina M.

Institute/workplace of the presenter

Department of Biophysics and Radiation Biology, Semmelweis University

Authors

Cristina M. Șulea¹, Dominik Sziklai¹, Miklós Pólos², Kálmán Benke², Zoltán Szabolcs², Miklós S.Z. Kellermayer¹

1: Department of Biophysics and Radiation Biology, Semmelweis University
2: Semmelweis University Heart and Vascular Center

Text of the abstract

Introduction: Fibrillin-1 microfibrils are essential for the assembly of elastic fibers and are critically involved in extracellular matrix homeostasis within connective tissues. In Marfan syndrome (MFS), mutations in the FBN1 gene lead to microfibrillar disruption, resulting in systemic connective tissue dysfunction and particularly high risk of aortopathy. We have previously shown that MFS affected fibrillin-1 microfibrils exhibit an overall thinner architecture compared to their non-MFS counterparts. Still, the consequences of FBN1 mutations on their nanomechanical characteristics are not yet known.
Aims: To explore the elastic properties of single fibrillin-1 microfibrils in human aortic tissue with and without Marfan syndrome.
Methods: The cohort consisted of 22 human subjects (12 MFS, 10 non-MFS). Fibrillin-1 microfibrils were extracted from aortic wall tissue and investigated for elasticity with atomic force microscopy. Young’s moduli (E) of the bead regions of fibrillin-1 microfibrils were calculated from force curves recorded in force mapping mode.
Result: 4,288 beads from 309 individual fibrillin-1 microfibrils were included. Mean E values ranged from 2.14±1.06 to 3.53±1.67 MPa in the MFS group and from 2.61±1.03 to 3.63±1.43 MPa in the non-MFS group. The MFS sample had slightly lower mean E compared to the non-MFS group (2.80 ± 1.22 MPa vs. 2.95 ± 1.29 MPa, p < 0.0001). Variability was higher within the MFS group.
Conclusion: We investigated the nanomechanical characteristics of human aorta-derived fibrillin-1 microfibrils. Elasticity was heterogeneously distributed in the MFS group and is probably dependent on the type of FBN1 mutation. The found differences in elastic properties may suggest additional mechanisms that lead to MFS-specific symptomatology.
Funding: The present research was funded by grants from the National Research, Development and Innovation Office of Hungary (ÚNKP-23-3-II-SE-22 to C.M.Ș., FK145928 to K.B., and K135360 to M.S.Z.K.), the European Union (RRF-2.3.1-21-2022-00003), and the SE 250+ Excellence PhD Scholarship.