Design of a microfluidic device to quantify dynamic intra-nuclear deformation during cell migration through confining...

Area of Science:

• Cell Biology
• Biophysics
• Biomaterials

Background:

• Cell migration is vital for tissue homeostasis, immune response, and cancer metastasis.
• Nuclear deformation during 3-D migration is increasingly studied, particularly the role of lamin A/C in cancer.
• Existing methods for studying cell migration in confined 3-D environments lack precision and physiological relevance.

Purpose of the Study:

• To develop a microfluidic device for precise control over cell confinement and high-resolution imaging of 3-D migration.
• To quantitatively measure nuclear deformation dynamics during cell migration through constrictions.
• To investigate the role of lamin A/C in nuclear deformability and cell migration through confined spaces.

Main Methods:

• Design and fabrication of a polydimethylsiloxane (PDMS) microfluidic device with precisely defined constrictions.
• Utilizing the device for live and fixed cell imaging with high resolution.
• Establishing long-lasting chemotactic gradients within the device without continuous perfusion.
• Quantitative analysis of dynamic nuclear deformation during cell migration.

Main Results:

• The microfluidic device enabled detailed imaging of nuclear translocation, lamina buckling, and intranuclear strain during cell migration.
• Lamin A/C-deficient cells showed increased and more plastic nuclear deformations compared to wild-type cells.
• Reduced lamin A/C levels enhanced cell migration through constrictions by increasing nuclear deformability, not compressibility.

Conclusions:

• The developed microfluidic device offers a powerful tool for studying intracellular mechanics in physiologically relevant confined environments.
• Low lamin A/C levels enhance cell invasion by increasing nuclear deformability.
• This approach has broad applications in studying cancer cell invasion and immune cell recruitment.