Modulating a Massive Set of Biomolecular Structures by Sono-Mechanical Force

Area of Science:

• Biophysics
• Molecular Biology
• Biomedical Engineering

Background:

• Single-molecule techniques like optical tweezers manipulate biomolecules but are limited in scale and cellular application.
• Existing methods face challenges in achieving high sensitivity and efficacy for force-based molecular manipulation, especially within living cells.

Purpose of the Study:

• To develop a scalable, non-intrusive method for generating sono-mechanical forces to manipulate biomolecular structures.
• To investigate the potential of low-power ultrasound for reversible unfolding of DNA structures and targeted drug delivery within cells.

Main Methods:

• Utilized low-power ultrasound (<5.3 mW cm⁻²) to generate sono-mechanical forces, calibrated against optical tweezers.
• Applied sono-mechanical forces to unfold DNA structures (G-quadruplexes, hairpins) and observed drug release from DNA carriers in cancer cells.

Main Results:

• Quantified sono-mechanical forces of at least 29 pN at 5.3 mW cm⁻², capable of simultaneously and reversibly unfolding multiple DNA structures.
• Demonstrated in-cell sono-mechanical unfolding, leading to doxorubicin release from DNA hairpin carriers and subsequent targeted cancer cell death.

Conclusions:

• Low-power ultrasound provides a flexible, non-intrusive method for manipulating large populations of biomolecules without fixed orientations.
• This sono-mechanical platform shows significant potential for applications in molecular biophysics, smart materials, and precision cancer medicine.