Biophysical Society Thematic Meeting | Singapore

Mechanobiology of Disease

Poster Abstracts

33-POS Board 33 Protection of Nuclear Morphology by the Lamin A/C-Mediated Organization of the Perinuclear Actin Cables

Dong-Hwee Kim , Jung-Won Park. Korea University, Seoul, South Korea.

Recent studies have shown a pronounced correlation between defects in nuclear morphology and the progression of diverse human diseases such as laminopathies, a set of diseases induced by mutations in the LMNA gene encoding nuclear lamin A/C. The perinuclear actin cables, simply actin cap, composed of highly contractile actomyosin lament bundles on top of the nucleus is bridged to lamin A/C of the nuclear lamina through LINC complexes. The distinct spatial organization of the actin cap facilitates rapid communication between extracellular physical stimuli and intracellular responses, including nuclear shaping and mechanotransduction of external forces into biophysical signals. These functions are abrogated in lamin A/C-decient mouse embryonic broblasts, a mouse model of the laminopathies, following disruption of the actin cap. However, how lamin A/C mediates the ability of the actin cap to regulate nuclear morphology in response to external mechanical stimuli remains unclear. Here, we develop a computational model to understand physical interactions between the cytoskeletal network and the nucleus in cellular mechano-responses, where each cellular component is analyzed discretely in a three-dimensional nite element model. The model explores the role of actin-cap-mediated mechanotransduction in maintaining nuclear morphology. Here, we show that lamin A/C harnesses the actin cap to protect nuclear morphology from extracellular physical disturbances.

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