Imaging self-assembly dependent spatial distribution of small molecules in a cellular environment

Area of Science:

• Biochemistry
• Cell Biology
• Materials Science

Background:

• Small molecule self-assembly is a common cellular process with significant biological implications.
• The behavior and impact of self-assembling small molecules within cellular environments remain largely unexplored.

Purpose of the Study:

• To investigate how enzyme-instructed self-assembly of small peptidic molecules influences their distribution and behavior within cells.
• To explore the potential of modulating cellular phenotypes through controlled self-assembly.

Main Methods:

• Synthesis of four fluorescent peptidic molecules with varying fluorophores and an enzyme trigger.
• Utilizing fluorescent imaging to observe molecular distribution in cellular environments.
• Conducting cell viability tests to assess the impact of molecular assemblies on cell phenotypes.
• Employing enzyme-instructed self-assembly (EISA) for spatiotemporal control.

Main Results:

• The studied molecules exhibited differential self-assembly capabilities before and after enzymatic transformation (dephosphorylation).
• Self-assembly significantly impacted the spatial distribution of small molecules within cells.
• Cellular phenotypes were demonstrably controlled by the state and location of molecular assemblies.
• One molecule's nanofibers stabilized actin filaments, mitigating the effects of a toxin.

Conclusions:

• Self-assembly is a critical determinant of small molecule spatial distribution in cellular systems.
• Enzyme-instructed self-assembly provides a viable strategy for modulating small molecule spatiotemporal profiles.
• This approach enables the utilization of emergent molecular properties to control cellular fate.