Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Poster Abstracts

44-POS Board 11 WHY WE SHOULD STUDY PROTEIN BINDING TO BICONTINUOUS INVERTED CUBIC PHASES, TO BETTER UNDERSTAND MEMBRANE TRAFFICKING. David P Siegel 1 ; 1 Givaudan Inc., 1199 Edison Drive, Cincinnati, OH, USA The membrane binding constants of proteins are sensitive to membrane curvature. This is true of some adaptors/effectors in the vesicle budding and fusion stages of membrane trafficking. Recently, others showed that some proteins bind preferentially to membranes with Gaussian curvature: they bind much more strongly to spherical vesicles (with positive Gaussian curvature) than to tubules with the same mean curvature but zero local Gaussian curvature. Fusion and fission pores in budding & fusion have special curvature properties. Here I show that the Gaussian curvature, range of mean curvature, and mean curvature gradient on the surfaces of such pores are different than in the membrane systems conventionally used to assess protein curvature sensing and induction (vesicles and the insides of tubules pulled from GUVs or cells). This is true for both symmetric membranes and asymmetric biomembranes. However, the curvature properties of bicontinuous inverted cubic (Q II ) phases are quite similar to those of pores. Q II phases and pores both have negative Gaussian curvature, true of neither vesicles nor tubules; have more negative mean curvature than many tubules; and gradients in mean curvature that are either absent or smaller in vesicles and tubules. It's been shown that proteins with molecular weights of several tens of kDa can enter the water channel networks in Q II phases, and that the phases can be equilibrated with peptides through the aqueous phase. This suggests that we might find new adaptors/effectors of trafficking by studying binding of peptides to Q II phases, compared to flat membranes of similar composition. Some features of Q II phases make such experiments awkward. Only certain ranges of lipid compositions form Q II phases, and, in phospholipids, temperature-cycling techniques or particular electrolyte compositions may be needed. Appropriate protocols will be proposed.

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