Presentation Information
[11a-B31-5]Substrate-Modulated Nanoendoscopy-AFM of Nuclear Mechanotransduction in Contractile Cells
〇ALEXIS BOROWIAK1,2, TAKEHIKO ICHIKAWA1,2, YOHEI KONO1,2, TAKESHI SHIMI1,5, MASAMICHI ITO3, RYO NITTA4, TAKESHI FUKUMA1,2 (1.Kanazawa Univ., 2.NanoLSI, 3.The Univ. of Tokyo, 4.Kobe Univ., 5.Cancer Res. Inst.)
Keywords:
Nanoendoscopy-AFM,HiPS-Cardiomyocytes,Substrate modulation
Understanding the mechanical properties of the nuclear envelope is crucial for cardiovascular diseases, especially laminopathies—genetic disorders caused by LMNA mutations that affect lamins A and C. These mutations weaken the nuclear lamina, making nuclei softer and more vulnerable to mechanical stress. We use Nanoendoscopy-Atomic Force Microscopy (AFM), a technique that uses a nano-needle tip to probe a cell’s interior for 3D mapping and mechanical analysis. In this study, we measure nuclear stiffness in beating hiPSC-derived cardiomyocytes and compare elasticity across cell types using Direct Nuclear Elasticity Measurements (DNEM) via Nanoendoscopy-AFM. Our findings confirm nuclear softening and support the role of the Sun2 inner nuclear membrane protein in connecting the nucleus to the cytoskeleton, advancing understanding of these diseases. This work will introduce the modulation of the biomechanical environment to distinguish mechanical stress effects from genetic factors, thereby providing a more physiologically relevant insight into nuclear fragility in contractile cells.
