Actomyosin, vimentin and LINC complex pull on osteosarcoma nuclei to deform on micropillar topography

Area of Science:

• Cell Biology
• Biophysics
• Biomaterials Science

Background:

• Cell deformation is crucial for processes like immune response and cancer metastasis.
• Nuclear deformation mechanisms during cell passage through constrictions remain poorly understood.
• Key factors and force direction (push vs. pull) in nuclear deformation are unclear.

Purpose of the Study:

• To elucidate the biochemical actors and forces driving nuclear deformation in confined environments.
• To utilize tunable poly-L-lactic acid micropillar topography to mimic in vivo constrictions.
• To establish a comprehensive model for cellular and nuclear deformation.

Main Methods:

• Employing poly-L-lactic acid micropillar arrays to simulate in vivo constrictions.
• Utilizing biochemical inhibitors to assess the role of specific cellular components.
• Manipulating micropillar adhesiveness to differentiate between pulling and pushing forces.
• Validating findings with an in silico cell model.

Main Results:

• Actomyosin contractility, vimentin, and nucleo-cytoskeletal connections are essential for nuclear deformation.
• A-type lamins do not play a significant role in this process.
• Chemically tuned micropillar adhesiveness demonstrated that pulling forces predominantly drive nuclear deformation.
• In silico modeling corroborated the experimental findings.

Conclusions:

• A comprehensive mechanism for cellular and nuclear deformation during confinement has been proposed.
• Microstructured biomaterials offer a versatile platform for studying force exertion in biological systems.
• These findings aid in dissecting and mimicking complex in vivo cellular behaviors.