Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Poster Abstracts

24-POS Board 8 DELINEATING THE SHAPE OF THE MEMBRANE BUD INDUCED BY PROTEIN COAT ASSEMBLIES

Sanjoy Paul 1 ; Qiang Cui 1,2,3 ; 1 Boston University, Department of Chemistry, Boston, MA, USA 2 Boston University, Department of Physics, Boston, MA, USA 3 Boston University, Department of Biomedical Engineering, Boston, MA, USA

Curvature generating proteins assemble on the membrane surface to bud vesicles for transporting protein cargoes from one cellular compartment to the other. Many of these proteins initiate the curvature induction by inserting their helical amphipathic regions where hydrophobic and hydrophilic residues are partitioned at the membrane water interface. Our latest research on the COPII molecular machinery protein Sar1 revealed that, in addition to the protein's penetration depth, the ability to bend the membrane surface is controlled by the volume inclusion of the protein inside the membrane. However, after initiating the curvature induction, what determines the shape of the membrane bud remains an open question. In vitro experiments reveal that a high concentration of Sar1 results in a tubular growth on the GUV whereas in vivo COPII coated vesicles are spherical in nature. Importantly, Sar1 together with Sec23/24 form the inner-coat assemblies where it is unknown whether Sec23/24 also contribute to the curvature induction. We hypothesize that Sec23/24 functions as a spacer to modulate the distribution and orientation of Sar1 proteins and therefore the shape of the membrane bud. We employ the dynamical triangulated surface simulation to model inner-coat assembly, where the membrane is viewed as a surface-enclosed triangular mesh, and the Helfrich Hamiltonian governs its dynamics with non zero intrinsic curvature at the protein containing mesh vertices. We reveal that the anisotropic protein membrane coupling leads to a disc like shape of the membrane bud while isotropic interactions give rise to a more spherical budding. Additionally, we dope some of the protein containing regions with zero intrinsic curvature to represent Sec23/24 and its impact on membrane shape. Overall, our analyses emphasize the importance of considering the orientations of a collection of amphipathic helices and the shape of the membrane bud.

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