How Membrane Geometry Regulates Protein Sorting Independently of Mean Curvature

Jannik B Larsen; Kadla R Rosholm; Celeste Kennard; Søren L Pedersen; Henrik K Munch; Vadym Tkach; John J Sakon; Thomas Bjørnholm; Keith R Weninger; Poul Martin Bendix; Knud J Jensen; Nikos S Hatzakis; Mark J Uline; Dimitrios Stamou

doi:10.1021/acscentsci.0c00419

How Membrane Geometry Regulates Protein Sorting Independently of Mean Curvature

ACS Cent Sci. 2020 Jul 22;6(7):1159-1168. doi: 10.1021/acscentsci.0c00419. Epub 2020 Jun 23.

Authors

Jannik B Larsen^{1

2

3

4}, Kadla R Rosholm^{1

2

3

4}, Celeste Kennard⁵, Søren L Pedersen^{3

4}, Henrik K Munch^{3

4}, Vadym Tkach^{1

2

3

4}, John J Sakon⁶, Thomas Bjørnholm^{1

2

3

4}, Keith R Weninger⁶, Poul Martin Bendix⁷, Knud J Jensen^{3

4}, Nikos S Hatzakis^{1

2

3

4}, Mark J Uline^{8

9}, Dimitrios Stamou^{1

2

3

4

9}

Affiliations

¹ Bionanotecnology and Nanomedicine Laboratory, University of Copenhagen, Copenhagen, Denmark.
² Nano-Science Center, University of Copenhagen, Copenhagen, Denmark.
³ Lundbeck Foundation Center Biomembranes in Nanomedicine, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Chemistry, University of Copenhagen, Copenhagen, Denmark.
⁵ Department of Chemical Engineering, University of South Carolina, Columbia, South Carolina, United States.
⁶ Department of Physics, North Carolina State University, Raleigh, North Carolina, United States.
⁷ Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
⁸ Department of Chemical Engineering, Biomedical Engineering Program, University of South Carolina, Columbia, South Carolina, United States.
⁹ Center for Geometrically Engineered Cellular Systems, University of Copenhagen, Copenhagen, Denmark.

Abstract

Biological membranes have distinct geometries that confer specific functions. However, the molecular mechanisms underlying the phenomenological geometry/function correlations remain elusive. We studied the effect of membrane geometry on the localization of membrane-bound proteins. Quantitative comparative experiments between the two most abundant cellular membrane geometries, spherical and cylindrical, revealed that geometry regulates the spatial segregation of proteins. The measured geometry-driven segregation reached 50-fold for membranes of the same mean curvature, demonstrating a crucial and hitherto unaccounted contribution by Gaussian curvature. Molecular-field theory calculations elucidated the underlying physical and molecular mechanisms. Our results reveal that distinct membrane geometries have specific physicochemical properties and thus establish a ubiquitous mechanistic foundation for unravelling the conserved correlations between biological function and membrane polymorphism.

Grants and funding

P20 GM103499/GM/NIGMS NIH HHS/United States