Unveiling the Electrical Properties of Hyaluronan-Coated Cancer Extracellular Vesicles Using Correlative Scanning...

Area of Science:

• Biophysics
• Nanotechnology
• Cancer Biology

Background:

• Cancer cells secrete extracellular vesicles (EVs) coated with hyaluronan (HA).
• Hyaluronan is a known cancer biomarker.
• Distinct electrical properties of EVs could aid in cancer detection.

Purpose of the Study:

• To investigate the electrical properties of hyaluronan-coated EVs using advanced scanning probe microscopy (SPM).
• To differentiate cancer EVs (CEVs) from normal EVs (NEVs) based on their electrical characteristics.
• To explore the potential of these methods for developing EV-based bioelectronic sensors.

Main Methods:

• Utilized multiple SPM-based nanoelectrical modes: electrostatic force microscopy (EFM), Kelvin probe force microscopy (KPFM), piezoresponse force microscopy (PFM), and conductive atomic force microscopy (C-AFM).
• Performed single-vesicle resolution analysis of electrical properties including surface potential, charge distribution, and piezoelectric response.
• Investigated ion-driven electron transport in sandwiched EV junctions.

Main Results:

• Distinct electrical properties were observed for different EV sets at the single-vesicle level.
• Surface potential, charge distribution, and piezoelectric electro-mechanical response varied between EV types.
• Electron transport in EV junctions was primarily ion-driven.
• The correlative SPM approach successfully distinguished HA-coated CEVs from NEVs.
• A label-free, multiplexed solution for assessing EV electrical properties was demonstrated.

Conclusions:

• Advanced SPM nanoelectrical modes provide a comprehensive, label-free method for characterizing EV electrical properties.
• This approach enables differentiation between cancer EVs and normal EVs.
• The findings support the development of novel EV-based bioelectronic sensors for cancer diagnostics.