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Endocytosis-Like Vesicle Fission Mediated by a Membrane-Expanding Molecular Machine Enables Virus Encapsulation for In Vivo Delivery.

Noriyuki UchidaYunosuke RyuYuichiro TakagiKen YoshizawaKotono SuzukiYasutaka AnrakuItsuki AjiokaNaofumi ShimokawaMasahiro TakagiNorihisa HoshinoTomoyuki AkutagawaTeruhiko MatsubaraToshinori SatoYuji HiguchiHiroaki ItoMasamune MoritaTakahiro Muraoka
Published in: Journal of the American Chemical Society (2023)
Biological membranes are functionalized by membrane-associated protein machinery. Membrane-associated transport processes, such as endocytosis, represent a fundamental and universal function mediated by membrane-deforming protein machines, by which small biomolecules and even micrometer-size substances can be transported via encapsulation into membrane vesicles. Although synthetic molecules that induce dynamic membrane deformation have been reported, a molecular approach enabling membrane transport in which membrane deformation is coupled with substance binding and transport remains critically lacking. Here, we developed an amphiphilic molecular machine containing a photoresponsive diazocine core (AzoMEx) that localizes in a phospholipid membrane. Upon photoirradiation, AzoMEx expands the liposomal membrane to bias vesicles toward outside-in fission in the membrane deformation process. Cargo components, including micrometer-size M13 bacteriophages that interact with AzoMEx, are efficiently incorporated into the vesicles through the outside-in fission. Encapsulated M13 bacteriophages are transiently protected from the external environment and therefore retain biological activity during distribution throughout the body via the blood following administration. This research developed a molecular approach using synthetic molecular machinery for membrane functionalization to transport micrometer-size substances and objects via vesicle encapsulation. The molecular design demonstrated in this study to expand the membrane for deformation and binding to a cargo component can lead to the development of drug delivery materials and chemical tools for controlling cellular activities.
Keyphrases
  • drug delivery
  • machine learning
  • high resolution
  • transcription factor
  • mass spectrometry
  • drinking water
  • protein protein
  • disease virus