Grafting Charged Species to Membrane-Embedded Scaffolds Dramatically Increases the Rate of Bilayer Flipping
نویسندگان
چکیده
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.
منابع مشابه
Dynamic membrane protein topological switching upon changes in phospholipid environment.
A fundamental objective in membrane biology is to understand and predict how a protein sequence folds and orients in a lipid bilayer. Establishing the principles governing membrane protein folding is central to understanding the molecular basis for membrane proteins that display multiple topologies, the intrinsic dynamic organization of membrane proteins, and membrane protein conformational dis...
متن کاملPreparation and Characterization of Microfiltration Membrane Embedded with Silver Nano-Particles
The microfiltration 0.2 µm Cellulose Acetate (CA) membrane was modified by embedding antibacterial silver nano-particles in the membrane pores. This novel technique was developed to enhance the capability of the microfiltration membrane for removing microorganism including bacteria. The prepared membrane was characterized using Scanning Electron Microscopy (SEM), Energy-Dispersive X-ray Spe...
متن کاملEvidences for a new cation channel in the brain mitochondrial inner membrane
Introduction: Previous studies and our works have indicated several cation channels in the rat brain mitochondrial inner membrane. In this work, we report the single-channel characterization of a cation channel from the rat brain mitochondrial inner membrane incorporated into a planar lipid bilayer. Methods: After removing and homogenizing the adult rat brain, its supernatant was centrifuged...
متن کاملCharacterization of biophysical properties of single chloride channel in rat brain mitochondrial inner membrane by channel incorporation into bilayer lipid membrane
Introduction: Recent studies have shown the presence of Cl- channels in heart and liver mitochondrial membranes. In this work, we have characterized the functional profile of a Cl- channel from rat brain mitochondria. Methods: After removing and homogenizing the rat brain, the supernatant was separately centrifuged in MSEdigitonin, H2O and Na2CO3 and mitochondrial inner membrane vesicles wer...
متن کاملComparison of Grafting Success Rate and Hearing Outcomes between Primary and Revision Tympanoplasties
Introduction: There are a few studies that compare the outcomes between primary and revision tympanoplasties. The purpose of the present study was to compare the results of type I tympanoplasty (i.e., synonymous to myringoplasty) and revision myringoplasty based on the closure of tympanic membrane perforation and hearing improvement. Materials and Methods: Thisprospective single-blind study was...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 3 شماره
صفحات -
تاریخ انتشار 2017