Intracellularly Self-Assembled 2D Materials Induce Apoptotic Cell Death by Impeding Cytosolic Transport

Area of Science:

• Biomaterials Science
• Cell Biology
• Nanotechnology

Background:

• 2D materials are typically introduced into cells via endocytosis, often resulting in insufficient lateral size to impede intracellular transport.
• Previous methods struggled to achieve significant intracellular 2D material accumulation, limiting their biological impact.

Purpose of the Study:

• To develop a method for generating oversized 2D materials within the cytosol of living cells.
• To investigate the impact of these intracellular 2D materials on cellular transport and viability.
• To explore the potential of these materials for novel therapeutic applications.

Main Methods:

• Utilized a photochemically isomerizable cucurbit[6]uril derivative as a building block for controlled self-assembly.
• Employed fluorescence recovery after photobleaching (FRAP) assays to assess the hindrance to intracellular transport.
• Used flow cytometry to correlate building block concentration, 2D material size, and cell viability.

Main Results:

• Successfully generated large, oversized 2D materials within the cytosol of living cells via controlled self-assembly.
• Demonstrated that these 2D materials significantly hindered both diffusive spreading and motor-driven motion of intracellular components.
• Established a threshold concentration of the building block required to impede cytosolic transport and induce apoptotic cell death, unlike endocytosed materials.

Conclusions:

• Intracellularly generated 2D materials can effectively alter cytosolic transport dynamics, leading to cell death.
• This approach overcomes limitations of endocytosis for achieving biologically significant intracellular 2D material accumulation.
• The findings open avenues for new therapeutics targeting drug resistance and intracellular platforms for studying intractable diseases.