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Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
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The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
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Ligand-gated ion channels are transmembrane proteins with a channel for ions to pass through and a binding site for a ligand. The channel opens only when a ligand attaches to the binding site.
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Mechanisms of Membrane Domain Formation00:59

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Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
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The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
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The living membranes are flexible due to their fluid mosaic nature; however, their bending into different shapes is an active process regulated by specific lipids and proteins. The membrane bending can be transient as seen in vesicles or stable for a long time as in microvilli. Cells regulate the size, location, and duration of the membrane curvature.
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Interaction between mechanosensitive channels embedded in lipid membrane.

Liangliang Zhu1, Wei Zhao2, Yuan Yan2

  • 1Shaanxi Institute of Energy and Chemical Engineering, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; State Key Laboratory for Strength and Vibration of Mechanical Structures, School of Aerospace, Xi'an Jiaotong University, Xi'an, 710049, China.

Journal of the Mechanical Behavior of Biomedical Materials
|November 30, 2019
PubMed
Summary

Mechanosensitive channels of small conductance (MscS) gating is influenced by membrane curvature and nearby mechanosensitive channels of large conductance (MscL). Local curvature delays MscS opening, while MscL molecules may aggregate in curved membrane regions.

Keywords:
Cooperative gatingLocal membrane curvatureMechanotransductionMscL localizationMscS

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Area of Science:

  • Biophysics
  • Molecular Biology
  • Computational Biology

Background:

  • Mechanosensitive channels (MSCs) are crucial for cellular responses to mechanical stimuli.
  • Understanding the gating mechanisms of MSCs, like MscS, is key to cellular adaptation.
  • Lipid membrane properties significantly influence protein behavior and function.

Purpose of the Study:

  • To investigate the gating behavior of MscS in Escherichia coli under mechanical stress.
  • To explore the role of local membrane curvature and neighboring MscL molecules on MscS function.
  • To elucidate the interplay between MSCs and the lipid bilayer at structural and physical levels.

Main Methods:

  • Utilized a molecular dynamics-decorated finite element method (MDeFEM) for simulations.
  • Incorporated local membrane curvature and multiple MscL molecules near MscS.
  • Simulated membrane stretch and global bending scenarios.

Main Results:

  • Local membrane curvature was found to delay MscS opening, with this effect diminishing upon stretching.
  • Both upward and downward membrane bending activated MscS when the curvature radius reached 34 nm, mimicking lysophosphatidylcholine insertion.
  • Multiple MscL molecules were observed to aggregate in the local membrane curvature zone around MscS, suggesting trapping by curvature.

Conclusions:

  • Local membrane curvature and neighboring MscL molecules play significant roles in regulating MscS gating.
  • MscL molecules can be localized by membrane curvature, influencing the MscS environment.
  • The study provides structural and physical insights into MSC-lipid interactions, offering predictions for future experiments.