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A BW Reporter System for Studying Receptor-Ligand Interactions
Published on: January 7, 2019
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Entropic Control of Receptor Recycling Using Engineered Ligands
Andre C M DeGroot1, David J Busch1, Carl C Hayden1
1Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas.
Biophysical Journal
|March 29, 2018
Summary
Receptor size, not just protein interactions, controls cellular uptake. Increasing receptor bulk via large ligands significantly reduces endocytosis, revealing a physical mechanism for regulating cell signaling and nutrient uptake.
Area of Science:
- Cell Biology
- Biophysics
- Molecular Biology
Background:
- Receptor internalization via endocytosis regulates cellular functions.
- Traditionally, protein interactions were thought to solely control receptor uptake.
- Emerging evidence suggests physical properties of receptors also influence internalization.
Purpose of the Study:
- To investigate how biochemical and biophysical factors jointly regulate receptor internalization.
- To determine the impact of receptor steric bulk on endocytic uptake.
- To establish a thermodynamic framework for receptor internalization.
Main Methods:
- Engineered variants of the transferrin receptor with increased steric bulk using large ligands.
- Analysis of receptor uptake probability by clathrin-coated structures.
- Thermodynamic modeling of receptor-vesicle binding energy and entropic costs.
Main Results:
- Increased steric bulk of receptors significantly decreases their uptake by clathrin-coated structures.
- Receptor uptake follows a thermodynamic trade-off between binding energy and entropic confinement.
- A universal scaling law predicts uptake based on membrane and endocytic structure occupancy, independent of receptor size.
Conclusions:
- Receptor size is a critical determinant of endocytic uptake, alongside biochemical interactions.
- A thermodynamic model accurately describes receptor internalization.
- Steric bulk modulation offers a biophysical strategy to control cell surface receptor levels for therapeutic applications.
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