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Biophysical modeling of membrane curvature generation and curvature sensing by the glycocalyx

Summary

The glycocalyx is a sugar-rich layer covering cells that helps cells interact and defend against infection. This research explains how the structure and density of glycocalyx molecules can physically bend and shape cell membranes by creating steric pressures. Scientists developed a mathematical model and confirmed through experiments that thicker glycocalyx layers generate more membrane curvature, and that these molecules preferentially accumulate in highly curved regions, suggesting they can sense membrane shape.

Background

The glycocalyx is a dense layer of glycosylated proteins and lipids on cell surfaces that mediates cell-cell interactions and pathogen protection. Recent experimental evidence shows that different membrane shapes are regulated by the glycocalyx, but a quantitative physical explanation of how glycocalyx properties determine membrane geometries remains lacking.

Objective

To develop a biophysical model based on polymer brush theory that explains how glycocalyx properties determine membrane curvature generation and to identify conditions under which the glycocalyx can both generate and sense membrane curvature.

Results

The model predicts that glycocalyx alone can generate membrane curvature independent of spontaneous curvature, with curvature generation dependent on grafting density and polymer backbone length. Experiments confirmed that filopodia density increases with glycan expression level. The model also predicts and experiments validate that glycocalyx exhibits curvature-sensing capabilities, preferentially partitioning to highly curved membrane regions.

Conclusion

This study establishes a quantitative biophysical framework linking glycocalyx properties to membrane curvature generation and sensing. The findings demonstrate that membrane shape is determined by competition between elastic energy, glycocalyx energy, and line tension, with glycocalyx polymers generating outward membrane bending through entropic forces rather than traditional mechanisms like wedging or scaffolding.
  • Published in:Proceedings of the National Academy of Sciences USA,
  • Study Type:Computational Modeling with Experimental Validation,
  • Source: PMID: 39969997, DOI: 10.1073/pnas.2418357122
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