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Related Concept Videos

Protein Diffusion in the Membrane01:24

Protein Diffusion in the Membrane

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Proteins show rotational as well as lateral diffusion across the membrane. The lateral diffusion of proteins was confirmed through the cell fusion experiment where mouse and human cells were fused, resulting in hybrid cells. When the human and mouse cells fused, the specific membrane proteins on human and mouse cells were marked with the red and green-fluorescent markers, respectively. Initially, the red and green fluorescence was located on the respective hemisphere of the cell. As time...
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Membrane Fluidity01:26

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Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is...
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Membrane Asymmetry Regulating Transporters01:19

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Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
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Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
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Regulation of Nuclear Protein Sorting01:45

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Facilitated Diffusion01:16

Facilitated Diffusion

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The plasma membrane, a critical structure in cellular biology, houses an array of transporters, or carrier proteins, interspersed within its lipid bilayer. These proteins play a crucial role in solute transport through facilitated diffusion, a form of passive diffusion that uses transporters to move the molecules across the membrane.
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Fluid Mosaic Model01:19

Fluid Mosaic Model

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Scientists identified the plasma membrane in the 1890s and its principal chemical components (lipids and proteins) by 1915. The model for plasma membrane structure, proposed in 1935 by Hugh Davson and James Danielli, was the first model to be widely accepted in the scientific community. The model was based on the plasma membrane's "railroad track" appearance in early electron micrographs. Davson and Danielli theorized that the plasma membrane's structure resembled a sandwich...
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Related Experiment Video

Updated: Jul 19, 2025

Spot Variation Fluorescence Correlation Spectroscopy for Analysis of Molecular Diffusion at the Plasma Membrane of Living Cells
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Spot Variation Fluorescence Correlation Spectroscopy for Analysis of Molecular Diffusion at the Plasma Membrane of Living Cells

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Heterogeneous biological membranes regulate protein partitioning via fluctuating diffusivity.

Ken Sakamoto1, Takuma Akimoto2, Mayu Muramatsu3

  • 1Department of System Design Engineering, Keio University, Yokohama, Kanagawa 223-8522, Japan.

PNAS Nexus
|August 18, 2023
PubMed
Summary

Cell membranes compartmentalize into ordered and disordered domains, influencing protein behavior. Simulations reveal how membrane heterogeneity affects protein diffusion and localization, crucial for cell signaling and trafficking.

Keywords:
anomalous diffusionbiological membranesfluctuating diffusivityheterogeneityphase separation

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Area of Science:

  • Biophysics
  • Cell Biology
  • Computational Biology

Background:

  • Cell membranes exhibit phase separation into ordered (liquid-ordered, Lo) and disordered (liquid-disordered, Ld) domains.
  • This heterogeneity regulates protein localization, impacting cell signaling and trafficking.
  • The effect of membrane heterogeneity on protein diffusion and localization remains poorly understood.

Purpose of the Study:

  • To investigate protein diffusion and localization in heterogeneous lipid bilayers with phase separation.
  • To elucidate the mechanisms governing protein partitioning between ordered and disordered membrane domains.
  • To explore the impact of molecular crowding and domain preference on protein dynamics.

Main Methods:

  • Langevin dynamics simulations coupled with the phase-field (LDPF) method.
  • Modeling heterogeneous biological membranes with distinct Lo and Ld domains.
  • Analyzing protein diffusion coefficients and partitioning behavior over millisecond timescales.

Main Results:

  • Protein diffusivity fluctuates temporally, influenced by local membrane composition.
  • Increased molecular concentration and domain preference lead to subdiffusive protein behavior.
  • Protein partitioning into Lo domains is quantitatively linked to diffusivity differences, domain preference, and concentration.

Conclusions:

  • Membrane heterogeneity significantly controls protein diffusion and localization dynamics.
  • Molecular crowding and confinement effects modulate protein mobility.
  • The findings provide insights into controlling biological reactions in heterogeneous membrane environments and offer a versatile simulation methodology for diverse systems.