Chromatin compaction during confined cell migration induces and reshapes nuclear condensates

Area of Science:

• Cell Biology
• Biophysics
• Cancer Research

Background:

• Cancer cell migration through narrow spaces necessitates significant nuclear deformation.
• Mechanical stress on the nuclear lamina and chromatin occurs during this process.
• The impact of mechanical deformation on subnuclear structures, particularly biomolecular condensates, remains poorly understood.

Purpose of the Study:

• To investigate how mechanical deformation of the nucleus affects subnuclear structures, specifically nuclear condensates.
• To understand the role of chromatin deformation in the assembly and properties of nuclear condensates during cell migration.
• To explore the relationship between chromatin heterogeneity and condensate formation in confined cell migration.

Main Methods:

• Studying cell migration through confined environments.
• Analyzing mechanical deformations of the chromatin network within the nucleus.
• Observing the behavior and coalescence of nuclear condensates (nucleoli, nuclear speckles).
• Investigating differential chromatin behavior in the advancing and trailing regions of the nucleus.

Main Results:

• Cell migration through constrictions deforms the chromatin network.
• Embedded nuclear condensates, including nucleoli and nuclear speckles, deform and coalesce due to chromatin deformation.
• Chromatin deformations differ between the nucleus's advancing and trailing regions.
• The trailing nuclear region shows increased permissiveness for new condensate formation due to heightened chromatin heterogeneity and a shifted binodal phase boundary.

Conclusions:

• Chromatin deformation during cell migration significantly impacts the assembly and properties of nuclear condensates.
• Differential chromatin behavior and heterogeneity in confined migration influence condensate dynamics.
• These findings highlight a mechanism for cellular mechanosensing involving chromatin and nuclear condensates.