-Motivated by single-molecule experiments on synaptic membrane protein domains, we use a stochastic lattice model to study protein reaction and diffusion processes in crowded membranes. We find that the stochastic reaction-diffusion dynamics of synaptic proteins provide a simple physical mechanism for collective fluctuations in synaptic domains, the molecular turnover observed at synaptic domains, key features of the single-molecule trajectories observed for synaptic proteins, and spatially inhomogeneous protein lifetimes at the cell membrane. Our results suggest that central aspects of the single-molecule and collective dynamics observed for membrane protein domains can be understood in terms of stochastic reaction-diffusion processes at the cell membrane.

Experiments have revealed that membrane proteins can form two-dimensional clusters with regular translational and orientational protein arrangements, which may allow cells to modulate protein function. However, the physical mechanisms yielding supramolecular organization and collective function of membrane proteins remain largely unknown. Here we show that bilayer-mediated elastic interactions between membrane proteins can yield regular and distinctive lattice architectures of protein clusters, and may provide a link between lattice architecture and lattice function. Using the mechanosensitive channel of large conductance (MscL) as a model system, we obtain relations between the shape of MscL and the supramolecular architecture of MscL lattices. We predict that the tetrameric and pentameric MscL symmetries observed in previous structural studies yield distinct lattice architectures of MscL clusters and that, in turn, these distinct MscL lattice architectures yield distinct lattice activation barriers. Our results suggest general physical mechanisms linking protein symmetry, the lattice architecture of membrane protein clusters, and the collective function of membrane protein lattices.

We numerically study the morphology of fluid membrane vesicles with the prescribed volume and surface area in confinement. For spherical confinement, we observe axisymmetric invaginations that transform into ellipsoidal invaginations when the area of the vesicle is increased, followed by a transition into stomatocyte-like shapes. We provide a detailed analysis of the axisymmetric shapes and investigate the effect of the spontaneous curvature of the membrane as a possible mechanism for shape regulation. We show that the observed morphologies are stable under small geometric deformations of the confinement. The results could help us to understand the role of mechanics in the complex folding patterns of biological membranes.

Protein-membrane interactions PACS 87.16.D--Membranes, bilayers, and vesicles PACS 34.20.-b -Interatomic and intermolecular potentials and forces, potential energy surfaces for collisionsAbstract -Membrane proteins deform the surrounding lipid bilayer, which can lead to membranemediated interactions between neighboring proteins. Using the mechanosensitive channel of large conductance (MscL) as a model system, we demonstrate how the observed differences in protein structure can affect membrane-mediated interactions and cooperativity among membrane proteins. We find that distinct oligomeric states of MscL lead to distinct gateway states for the clustering of MscL, and predict signatures of MscL structure and spatial organization in the cooperative gating of MscL. Our modeling approach establishes a quantitative relation between the observed shapes and cooperative function of membrane proteins.