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Updated: Sep 14, 2025
05:56
Spot Variation Fluorescence Correlation Spectroscopy for Analysis of Molecular Diffusion at the Plasma Membrane of Living Cells
Published on: November 12, 2020
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Local ligand concentration gradients induced by the plasma membrane
Ágnes Szabó1,2, Gabriella Tóth1, Tímea Szatmári1
1Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Iscience
|July 21, 2025
Summary
Ligand concentration near cell membranes is uneven, with peaks affecting receptor activation. This non-homogeneous distribution influences epidermal growth factor (EGF) receptor binding and signaling dynamics.
Area of Science:
- Cell biology
- Biophysics
- Biochemistry
Background:
- The plasma membrane is a dynamic environment where soluble ligands stimulate transmembrane proteins.
- The influence of the extracellular matrix and ligand distribution on receptor activation is often overlooked.
Purpose of the Study:
- To quantitatively measure epidermal growth factor (EGF) concentration at the cell membrane.
- To investigate the impact of non-homogeneous ligand distribution on receptor activation.
Main Methods:
- Quantitative measurements of EGF concentration at the cell membrane.
- Theoretical calculations and computational simulations.
- Experimental validation.
Main Results:
- Ligand distribution at the membrane is non-homogeneous, forming two concentration peaks.
- A membrane-proximal peak is attributed to membrane turnover.
- A more distant peak, observed in ErbB2-expressing cells, is linked to hindered diffusion possibly caused by the extracellular matrix.
- These phenomena alter receptor-ligand interactions, increasing apparent affinity and decreasing apparent cooperativity.
Conclusions:
- Non-homogeneous ligand concentration profiles at the cell membrane significantly impact receptor activation.
- The extracellular matrix and membrane dynamics contribute to ligand distribution.
- Understanding these spatial effects is crucial for interpreting receptor-ligand interactions and signaling.
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