Multimodal microscale mechanical mapping of cancer cells in complex microenvironments

Area of Science:

• Cellular mechanics and biophysics
• Cancer cell biology
• Biomaterials and tissue engineering

Background:

• Cell mechanical phenotype is crucial for survival under deformation.
• Cancer cells may adapt mechanical phenotypes to different geometries for survival.
• Disrupting this adaptability is a potential therapeutic strategy.

Purpose of the Study:

• To quantify the diversity of cancer cell mechanical states.
• To mimic in vitro extracellular matrix environments (2D and 3D).
• To investigate the relationship between cell shape and mechanical state.

Main Methods:

• Utilized Brillouin microscopy (GHz) and optical tweezer microrheology (7-15 kHz).
• Measured intracellular mechanics of cancer cells in 2D and 3D environments.
• Varied substrate stiffness, dimensionality, and fibrillar topography.

Main Results:

• Good agreement between Brillouin microscopy and optical tweezer microrheology.
• Confirmed correlation between modalities operating at different timescales.
• Cell shape heterogeneity correlates with mechanical state; spheroids show less heterogeneity than single cells.

Conclusions:

• Cancer cell mechanical phenotypes are diverse and environment-dependent.
• Mechanical cooperativity exists between cells within multicellular spheroids.
• Findings support targeting cancer cell mechanical plasticity.