Complex Deformation Characteristics of Liposomes during Atomic Force Microscopy Force Curves

Area of Science:

• Materials Science
• Nanotechnology
• Biophysics

Background:

• Liposomal doxorubicin nanoparticles (NPs) are crucial drug delivery systems.
• Accurate characterization of NP mechanical properties is essential for understanding their behavior in biological environments.
• Atomic Force Microscopy (AFM) is a powerful tool for nanoscale mechanical measurements.

Purpose of the Study:

• To quantify the shape and effective Young's modulus of liposomal doxorubicin NPs using AFM.
• To investigate the influence of measurement conditions (air vs. phosphate-buffered saline) on NP mechanical properties.
• To analyze uncertainties in AFM-derived Young's modulus measurements.

Main Methods:

• Atomic Force Microscopy (AFM) topography imaging and force curve analysis.
• Application of the Johnson-Kendall-Roberts (JKR) model to fit AFM force curve data.
• Monte Carlo uncertainty analysis to assess systematic uncertainties in measurements.

Main Results:

• Liposomal doxorubicin NPs exhibit significant shape changes, collapsing to 3 ± 1 nm in air and expanding to 27 ± 6 nm in PBS.
• The effective Young's modulus in PBS is 25 MPa (68% coverage interval [1.5-46] MPa) at the NP center.
• Edge measurements and environmental conditions (air vs. PBS) impact measured Young's modulus values.

Conclusions:

• AFM measurement conditions profoundly affect the characterization of soft nanoparticle mechanical properties.
• Systematic uncertainties in calibration parameters can lead to substantial bounds in modulus uncertainty.
• Careful consideration of experimental conditions and uncertainty analysis is critical for reliable AFM characterization of soft NPs.