Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping
The cell membrane is a barrier to the passive diffusion of charged molecules due to the chemical properties of the lipid bilayer. Surprisingly, recent experiments have identified processes in which synthetic and biological charged species directly transfer across lipid bilayers on biologically relev...
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| Format: | Article |
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American Chemical Society (ACS)
2017
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| Online Access: | http://hdl.handle.net/1721.1/111626 https://orcid.org/0000-0001-5554-1283 |
| _version_ | 1826197406610358272 |
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| author | Van Lehn, Reid C. Alexander-Katz, Alfredo |
| author2 | Massachusetts Institute of Technology. Department of Materials Science and Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Materials Science and Engineering Van Lehn, Reid C. Alexander-Katz, Alfredo |
| author_sort | Van Lehn, Reid C. |
| collection | MIT |
| description | The cell membrane is a barrier to the passive diffusion of charged molecules due to the chemical properties of the lipid bilayer. Surprisingly, recent experiments have identified processes in which synthetic and biological charged species directly transfer across lipid bilayers on biologically relevant time scales. In particular, amphiphilic nanoparticles have been shown to insert into lipid bilayers, requiring the transport of charged species across the bilayer. The molecular factors facilitating this rapid insertion process remain unknown. In this work, we use atomistic molecular dynamics simulations to calculate the free energy barrier associated with "flipping" charged species across a lipid bilayer for species that are grafted to a membrane-embedded scaffold, such as a membrane-embedded nanoparticle. We find that the free energy barrier for flipping a grafted ligand can be over 7 kcal/mol lower than the barrier for translocating an isolated, equivalent ion, yielding a 5 order of magnitude decrease in the corresponding flipping time scale. Similar results are found for flipping charged species grafted to either nanoparticle or protein scaffolds. These results reveal new mechanistic insight into the flipping of charged macromolecular components that might play an important, yet overlooked, role in signaling and charge transport in biological settings. Furthermore, our results suggest guidelines for the design of synthetic materials capable of rapidly flipping charged moieties across the cell membrane. |
| first_indexed | 2024-09-23T10:47:13Z |
| format | Article |
| id | mit-1721.1/111626 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T10:47:13Z |
| publishDate | 2017 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1116262022-09-27T15:02:01Z Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping Van Lehn, Reid C. Alexander-Katz, Alfredo Massachusetts Institute of Technology. Department of Materials Science and Engineering Alexander-Katz, Alfredo The cell membrane is a barrier to the passive diffusion of charged molecules due to the chemical properties of the lipid bilayer. Surprisingly, recent experiments have identified processes in which synthetic and biological charged species directly transfer across lipid bilayers on biologically relevant time scales. In particular, amphiphilic nanoparticles have been shown to insert into lipid bilayers, requiring the transport of charged species across the bilayer. The molecular factors facilitating this rapid insertion process remain unknown. In this work, we use atomistic molecular dynamics simulations to calculate the free energy barrier associated with "flipping" charged species across a lipid bilayer for species that are grafted to a membrane-embedded scaffold, such as a membrane-embedded nanoparticle. We find that the free energy barrier for flipping a grafted ligand can be over 7 kcal/mol lower than the barrier for translocating an isolated, equivalent ion, yielding a 5 order of magnitude decrease in the corresponding flipping time scale. Similar results are found for flipping charged species grafted to either nanoparticle or protein scaffolds. These results reveal new mechanistic insight into the flipping of charged macromolecular components that might play an important, yet overlooked, role in signaling and charge transport in biological settings. Furthermore, our results suggest guidelines for the design of synthetic materials capable of rapidly flipping charged moieties across the cell membrane. National Science Foundation (U.S.) (Award DMR-0819762) National Science Foundation (U.S.) (Award DMR-1054671) 2017-09-22T15:27:27Z 2017-09-22T15:27:27Z 2017-02 2016-11 2017-09-19T12:43:56Z Article http://purl.org/eprint/type/JournalArticle 2374-7943 2374-7951 http://hdl.handle.net/1721.1/111626 Van Lehn, Reid C., and Alexander-Katz, Alfredo. “Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping.” ACS Central Science 3, 3 (March 2017): 186–195 © 2017 American Chemical Society https://orcid.org/0000-0001-5554-1283 http://dx.doi.org/10.1021/ACSCENTSCI.6B00365 ACS Central Science Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) ACS |
| spellingShingle | Van Lehn, Reid C. Alexander-Katz, Alfredo Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping |
| title | Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping |
| title_full | Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping |
| title_fullStr | Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping |
| title_full_unstemmed | Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping |
| title_short | Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping |
| title_sort | grafting charged species to membrane embedded scaffolds dramatically increases the rate of bilayer flipping |
| url | http://hdl.handle.net/1721.1/111626 https://orcid.org/0000-0001-5554-1283 |
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