Geometrically constrained cytoskeletal reorganisation modulates DNA nanostructures uptake

Area of Science:

• Biomedical Engineering
• Cell Biology
• Nanotechnology

Background:

• DNA nanostructures (DNs) are increasingly used in biomedicine due to their programmability and low cytotoxicity.
• Understanding cellular uptake mechanisms is crucial for effective DN application.
• Existing research focuses on DN properties, neglecting cellular mechanical factors.

Purpose of the Study:

• To investigate the role of cellular mechanics and morphology in DNA nanostructure (DN) uptake.
• To explore how geometric constraints influence cell behavior and DN internalization.
• To identify strategies for enhancing DN delivery through cell manipulation.

Main Methods:

• Subjecting cells to geometric constraints to induce cytoskeletal remodeling.
• Analyzing changes in actin cytoskeleton organization (length, number, orientation of F-actin fibers).
• Measuring differential mechanical force generation and its correlation with DN uptake.

Main Results:

• Geometric constraints lead to actin cytoskeleton remodeling and distinct cell mechanophenotypes.
• Cellular mechanical forces, driven by F-actin reorganization, significantly facilitate DN uptake.
• DN uptake is directly governed by F-actin forces generated under geometric confinement.

Conclusions:

• Actin dynamics play a critical role in the cellular uptake of DNA nanostructures.
• Modulating cell morphology via geometric constraints can enhance DN internalization.
• This provides a novel strategy for optimizing therapeutic DN delivery systems.