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Gap Junction-Mediated Delivery of Polymeric Macromolecules
Andrea N Trementozzi1, Chi Zhao1, Hugh Smyth2
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, United States.
ACS Biomaterials Science & Engineering
|March 10, 2022
Summary
Gap junctions facilitate the transfer of large molecules like dextran (up to 40 kDa) between cells. Cell-derived vesicles called connectosomes efficiently deliver these membrane-impermeable molecules into the cell cytosol.
Area of Science:
- Cell Biology
- Biotechnology
- Molecular Medicine
Background:
- Cellular delivery of therapeutic macromolecules is hindered by inefficient plasma membrane transport.
- Gap junction channels, formed by connexin proteins, enable small molecule transfer.
- Emerging evidence suggests potential for larger molecule transfer, like microRNAs, via gap junctions.
Purpose of the Study:
- To provide direct evidence for gap junction-mediated transfer of polymeric macromolecules.
- To investigate the transport capacity of dextran chains through gap junctions.
- To evaluate the efficacy of connectosomes in delivering macromolecules into cells.
Main Methods:
- Examined dextran chain transport (10-70 kDa) across multiple cell layers.
- Assessed dextran loading into connectosomes by opening connexon hemichannel pores.
- Compared cytosolic delivery efficiency of dextran-loaded connectosomes versus free dextran.
Main Results:
- Dextran chains up to 40 kDa diffused through five cell layers in a gap junction-dependent manner within 30 minutes.
- 10 kDa dextran loaded into over 90% of connectosomes, with decreased loading for larger chains.
- Connectosomes significantly enhanced delivery of 10 kDa dextran into the cellular cytosol compared to free dextran.
Conclusions:
- Polymeric macromolecules can be delivered into cells via gap junctions.
- The gap junction pathway offers a promising route for therapeutic delivery of nucleic acids and peptides.
- Connectosomes represent an effective vehicle for intracellular delivery of membrane-impermeable molecules.
Keywords:
cellular deliveryconnectosomesconnexinsconnexon hemichannel poresgap junctionpolymeric macromoleculesMore Related Videos
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