4.8 Article

Release of content through mechano-sensitive gates in pressurized liposomes

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1001316107

Keywords

coarse-grained; molecular dynamics simulation; MARTINI force field; protein channel; drug delivery vehicle

Funding

  1. Marie Curie Research Training Network SizeDepEn
  2. Academy of Finland
  3. Netherlands Organization for Scientific Research

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Mechano-sensitive channels are ubiquitous membrane proteins that activate in response to increasing tension in the lipid membrane. They facilitate a sudden, nonselective release of solutes and water that safeguards the integrity of the cell in hypo-or hyper-osmotic shock conditions. We have simulated the rapid release of content from a pressurized liposome through a particular mechano-sensitive protein channel, MscL, embedded in the liposomal membrane. We show that a single channel is able to relax the liposome, stressed to the point of bursting, in a matter of microseconds. We map the full activation-deactivation cycle of MscL in near-atomic detail and are able to quantify the rapid decrease in liposomal stress as a result of channel activation. This provides a computational tool that opens the way to contribute to the rational design of functional nano-containers.

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