Using DNA Origami to Study Nanoscale Organization of Plasma Membranes

Area of Science:

• Cell Biology
• Biophysics
• Nanotechnology

Background:

• Plasma membrane (PM) nanodomains are crucial for cellular processes but are difficult to study due to their small size and instability.
• Understanding the organization and dynamics of these nanodomains is essential for deciphering cellular functions.

Purpose of the Study:

• To develop a novel method for visualizing and analyzing plasma membrane nanodomains in living cells.
• To investigate the role of the actin cytoskeleton and mechanical forces in regulating nanodomain organization.

Main Methods:

• Fabrication of fluorescent DNA origami probes with lipid anchors for insertion into the plasma membrane.
• Single-particle tracking of diffusing probes to survey membrane organization.
• Experimental manipulation including actin cytoskeleton disruption and cell stretching.

Main Results:

• DNA origami probe immobilization indicates simultaneous interaction with multiple nanodomains.
• Disruption of the actin cytoskeleton reduces probe immobilization, highlighting its role in nanodomain stability.
• Cell stretching reversibly alters probe mobility, demonstrating mechanical regulation of nanodomain organization.

Conclusions:

• The DNA origami approach offers precise control for studying plasma membrane nanodomain architecture and dynamics.
• This method provides new mechanistic insights into how cellular structures and external forces influence membrane organization.