Directing nuclear deformation on micropillared surfaces by substrate geometry and cytoskeleton organization

Area of Science:

• Biomaterials Science
• Cell Biology
• Cancer Research

Background:

• Nuclear deformation in osteosarcoma cells was previously observed on poly-L-lactic acid (PLLA) micropillar substrates.
• Understanding factors influencing nuclear deformation is crucial for cancer cell mechanics research.

Purpose of the Study:

• To investigate the impact of substrate properties and cell-type on nuclear deformation in osteosarcoma cells.
• To elucidate the role of cytoskeletal elements in modulating nuclear shape changes.

Main Methods:

• Utilized poly-L-lactic acid (PLLA) micropillar substrates with varied chemical, mechanical, and geometric properties.
• Assessed nuclear deformation in SaOs-2, MG-63, and OHS-4 osteosarcoma cell lines.
• Employed Atomic Force Microscopy (AFM)-based colloidal force spectroscopy to measure cell stiffness.
• Examined cytoskeletal organization (actin, microtubules, vimentin) using microscopy.

Main Results:

• Micropillar substrate's chemical and mechanical properties had minimal effect on nuclear deformation.
• Pillar size and spacing (geometry) significantly modulated SaOs-2 cell nucleus deformation.
• Distinct cell-type specific differences in nuclear deformation capacity were observed among SaOs-2, MG-63, and OHS-4 cells.
• Highly deformable SaOs-2 cells exhibited greater stiffness and prominent actin fibers, suggesting an actin-mediated mechanism.
• MG-63 and OHS-4 cells showed nuclear deformation facilitated by microtubule and vimentin networks, even with less prominent actin.

Conclusions:

• Substrate geometry is a primary driver of nuclear deformation, surpassing material properties.
• Cell phenotype and the organization of the actin, microtubule, and vimentin cytoskeletons are critical for efficient nuclear deformation.
• An interplay between cytoskeletal elements is necessary for optimal nuclear shape modulation in osteosarcoma cells.