Nonlinear temperature dependency of cell mechanics and consequences for potential filter applications

Area of Science:

• Biophysics
• Cell Mechanics
• Biomedical Engineering

Background:

• Label-free methods for isolating circulating tumor cells (CTCs) are crucial for cancer diagnostics.
• Previous research has overlooked the significant impact of temperature on cell mechanical properties relevant to filtration.

Purpose of the Study:

• To systematically investigate the temperature dependence of melanoma cell mechanical properties.
• To evaluate the potential of exploiting these temperature-dependent properties for CTC isolation using microfluidic filtration.

Main Methods:

• Atomic force spectroscopy was used to measure single A375 melanoma cell mechanics (Young's modulus, deformation, adhesion) across eight temperatures (15°C–39°C).
• Microfluidic experiments with filters of decreasing pore sizes were conducted to assess temperature-dependent cell capture and filtration efficiency.

Main Results:

• Melanoma cell stiffness, deformability, and adhesion exhibited strong, non-linear dependencies on temperature, independent of cell size.
• Between 17°C and 37°C, Young's modulus, deformation, and adhesion changed by factors of ~2.2, ~1.4, and ~2.7, respectively.
• Microfluidic filtration demonstrated that cells could penetrate smaller pores at higher temperatures, validating the mechanical property findings.

Conclusions:

• Cellular mechanical properties are highly sensitive to temperature variations within the physiological range.
• Temperature-controlled changes in cell mechanics offer a novel, label-free approach for selective CTC isolation.
• This study provides a comprehensive dataset and validates a new strategy for advancing CTC isolation technologies for cancer diagnostics.