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Published on: January 28, 2021
Rewiring Intercellular Communication with Self-Assembling Nanofibers
Ludovico Aloisio1,2, Vito Vurro2, Alberto D Scaccabarozzi1,2
1Dipartimento di Fisica, Politecnico di Milano,Piazza L. da Vinci 32, Milan 20133, Italy.
ACS Nano
|June 23, 2026
Summary
The small molecule DTTO self-assembles into nanofibers within cells, creating electrical connections between them. This restores intercellular communication, offering a new way to treat diseases without genetic modification.
Area of Science:
- Biophysics
- Cell Biology
- Biomaterials
Background:
- Intercellular electrical coupling via gap junctions is vital for biological signaling.
- Disrupted coupling contributes to various diseases, including cardiac and neurological disorders.
- Restoring cell-to-cell electrical communication non-genetically is a significant challenge.
Purpose of the Study:
- To investigate the potential of intracellular self-assembled nanofibers for restoring electrical coupling between cells.
- To establish a novel, non-genetic method for creating functional bioelectrical connections in situ.
Main Methods:
- Utilized the small conjugated molecule DTTO (2,6-diphenyl-3,5-dimethyl-dithieno[3,2-b:2',3'-d]thiophene-4,4-dioxide) which self-assembles into nanofibers inside cells.
- Employed dual patch clamp recordings to assess electrical coupling.
- Performed pharmacological suppression of native gap junctions for control experiments.
- Conducted electrical characterization including humidity-dependent measurements and impedance spectroscopy.
Main Results:
- DTTO nanofibers successfully formed and spanned between neighboring cells, connecting their cytoplasm.
- Functional electrical coupling was restored, demonstrated by signal transmission even when native gap junctions were inhibited.
- Control experiments ruled out nonspecific membrane poration as the cause of signal recovery.
- Electrical characterization confirmed that DTTO fiber networks support charge transport, influenced by ionic and interfacial factors.
Conclusions:
- Intracellular self-assembly of DTTO nanofibers provides a non-genetic strategy to create functional bioelectrical connections.
- This approach can restore electrical communication in cells, with potential applications in treating diseases and engineering tissues.
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