Surface morphometrics reveals local membrane thickness variation in organellar subcompartments

Area of Science:

• Cellular Biology
• Biophysics
• Structural Biology

Background:

• Lipid bilayers are fundamental to cellular architecture and organelle function.
• Previous studies on liposomes show lipid composition affects membrane properties like thickness and curvature.
• Characterizing these properties in native cellular environments has been challenging.

Purpose of the Study:

• To develop and apply a method for quantifying membrane thickness in native cellular contexts.
• To investigate variations in membrane thickness within and between organelles.
• To explore correlations between membrane thickness, curvature, and associated macromolecular complexes.

Main Methods:

• Utilized cellular cryo-electron tomography (cryo-ET) for high-resolution imaging.
• Expanded the 'Surface Morphometrics' pipeline to reconstruct and model membrane surfaces.
• Quantified membrane thickness by measuring the distance between phospholipid head groups (PHG).

Main Results:

• Demonstrated measurable thickness variations within and between different organellar membranes.
• Showed a positive correlation between membrane thickness and membrane curvedness.
• Identified varying membrane thicknesses in mitochondrial inner membrane subcompartments, independent of network morphology.
• Observed that large macromolecular complexes correlate with local membrane thickness variations.

Conclusions:

• The updated Surface Morphometrics pipeline enables quantitative analysis of native membrane ultrastructure.
• Membrane thickness is a variable property influenced by cellular context and potentially lipid composition.
• This framework facilitates research into how altered membrane properties affect organelle function in health and disease.