講演情報
[17a-PB3-8]Elucidating the Structural Hypothesis of Laminopathy in Contractile Cells via
Nanoendoscopy-Atomic Force Microscopy: Towards Substrate-Modulated Studies
〇ALEXIS BOROWIAK1,2, TAKEHIKO ICHIKAWA1,2, YOHEI KONO1,2, TAKESHI SHIMI1,2, MASAMICHI ITO3, RYO NITTA4, TAKESHI FUKUMA1,2 (1.Kanazawa Univ., 2.NanoLSI, 3.The Univ. of Tokyo, 4.Kobe Univ.)
キーワード：
Nanoendoscopy-AFM、HiPS-Cardiomyocytes、Hydrogels
Understanding the mechanical properties of the nuclear envelope is a key challenge in cardiovascular diseases, particularly in laminopathies—a group of genetic disorders caused by mutations in the LMNA gene (which encodes lamins A and C). The structural hypothesis of laminopathies posits that these mutations weaken the nuclear lamina, resulting in softer nuclei that are more susceptible to mechanical stress. To test this, we employ Nanoendoscopy-Atomic Force Microscopy (AFM). This recently developed technique employs a nano-needle-like tip to directly probe the interior of a cell, enabling 3D mapping and extraction of mechanical properties. In this study, we present our results on the measurement of nuclear stiffness in beating human-induced Pluripotent Stem Cell (hiPSC)-derived cardiomyocytes. We compare nuclear elasticity across different cardiomyocyte types using a new approach, Direct Nuclear Elasticity Measurements (DNEM)-Nanoendoscopy-AFM. The results provide direct evidence of lamina mechanical defects and nuclear fragility, thereby supporting the structural hypothesis of laminopathies and contributing to the fundamental understanding of these diseases. This work not only provides evidence supporting the structural hypothesis but also lays the groundwork for more advanced biomechanical studies. Given the observed link between substrate properties and cellular mechanics, the next generation of experiments involves modulating the biomechanical environment using hydrogel-based substrates of controlled stiffness. This approach is critical for decoupling mechanical stress effects from genetic factors, enabling a more physiologically relevant understanding of nuclear fragility in laminopathies.