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Updated: Oct 22, 2025

Screening for Amyloid Aggregation by Semi-Denaturing Detergent-Agarose Gel Electrophoresis
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Membrane composition and lipid to protein ratio modulate amyloid kinetics of yeast prion protein

Arnab Bandyopadhyay1, Achinta Sannigrahi1, Krishnananda Chattopadhyay1

  • 1Structural Biology & Bio-Informatics Division, CSIR-Indian Institute of Chemical Biology 4, Raja S. C. Mullick Road Kolkata 700032 India krish@iicb.res.in sannigrahiachinta@gmail.com.

RSC Chemical Biology
|August 30, 2021
PubMed

Insights

Yeast prion protein Sup35 aggregation is modulated by lipid concentration and membrane charge. Optimal lipid concentrations on zwitterionic membranes induced biphasic aggregation, unlike monophasic kinetics observed at other concentrations or on charged membranes.

Area of Science:

  • Biophysics
  • Neurodegenerative Diseases
  • Prion Biology

Background:

  • Prion aggregation in membranes is linked to neurodegenerative diseases.
  • Understanding these mechanisms is crucial for therapeutic development.

Purpose of the Study:

  • Investigate how membrane environment influences the aggregation of yeast prion protein Sup35.
  • Determine the role of lipid composition and lipid/protein ratio in prion aggregation kinetics.

Main Methods:

  • Utilized single-molecule resolution fluorescence correlation spectroscopy (FCS).
  • Employed complementary biophysical techniques.
  • Examined aggregation kinetics across various lipid compositions and protein-to-lipid ratios.

Main Results:

  • Lipid composition and lipid/protein ratio significantly modulate Sup35 aggregation kinetics.
  • Zwitterionic membranes (DMPC) showed biphasic aggregation at optimal lipid concentrations (OLC), but monophasic at low (LLC) and excess (ELC) concentrations.
  • Negatively charged membranes did not exhibit biphasic aggregation across any tested ratio.

Conclusions:

  • Membrane properties critically control prion protein aggregation pathways.
  • Findings offer mechanistic insights into how membrane-modulated aggregation contributes to neurodegenerative diseases.
  • Identified specific lipid concentration ranges influencing aggregation dynamics.

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