Fast, multi-frequency, and quantitative nanomechanical mapping of live cells using the atomic force microscope

Area of Science:

• Cellular Mechanobiology
• Nanoscale Biophysics
• Cancer Cell Biology

Background:

• Linking dynamic cellular processes to nanoscale mechanical properties requires high spatio-temporal resolution.
• Traditional Atomic Force Microscopy (AFM) has insufficient speed for dynamic cellular studies.
• Existing methods struggle to capture rapid changes in cell mechanics.

Purpose of the Study:

• To develop a quantitative mechanical microscopy method for live eukaryotic cells.
• To achieve high spatio-temporal resolution in mapping nanoscale mechanical properties.
• To improve AFM imaging throughput for studying dynamic cellular processes.

Main Methods:

• A novel technique enhancing commercial AFM systems for quantitative mapping of viscoelastic properties.
• Utilizing amplitude-modulation AFM (AM-AFM) principles with significantly reduced image acquisition times.
• Applying the method to MDA-MB-231 breast carcinoma cells treated with Syk inhibitors.

Main Results:

• Achieved ~20-fold improvement in nanomechanical imaging throughput compared to standard AM-AFM.
• Enabled quantitative mapping of dynamic viscoelastic properties at widely separated frequencies over large areas.
• Captured spatio-temporal mechanical responses of cancer cells to Syk inhibition.

Conclusions:

• The developed AFM technique offers a ~20x throughput increase for nanomechanical imaging.
• This method provides crucial insights into Syk signaling pathways regulating cancer cell motility.
• Enables real-time mechanical analysis of dynamic cellular processes within single cells.