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Mechanobiology of Disease
Poster Abstracts
110
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.