144 research outputs found
Recommended from our members
Modeling membrane nanotube morphology: the role of heterogeneity in composition and material properties.
Membrane nanotubes are dynamic structures that may connect cells over long distances. Nanotubes are typically thin cylindrical tubes, but they may occasionally have a beaded architecture along the tube. In this paper, we study the role of membrane mechanics in governing the architecture of these tubes and show that the formation of bead-like structures along the nanotubes can result from local heterogeneities in the membrane either due to protein aggregation or due to membrane composition. We present numerical results that predict how membrane properties, protein density, and local tension compete to create a phase space that governs the morphology of a nanotube. We also find that there exists a discontinuity in the energy that impedes two beads from fusing. These results suggest that the membrane-protein interaction, membrane composition, and membrane tension closely govern the tube radius, number of beads, and the bead morphology
Protein-induced membrane curvature changes membrane tension
Adsorption of proteins onto membranes can alter the local membrane curvature.
This phenomenon has been observed in biological processes such as endocytosis,
tubulation and vesiculation. However, it is not clear how the local surface
properties of the membrane, such as membrane tension, change in response to
protein adsorption. In this paper, we show that the classical elastic model of
lipid membranes cannot account for simultaneous changes in shape and membrane
tension due to protein adsorption in a local region, and a viscous-elastic
formulation is necessary to fully describe the system. Therefore, we develop a
viscous-elastic model for inhomogeneous membranes of the Helfrich type. Using
the new viscous-elastic model, we find that the lipids flow to accommodate
changes in membrane curvature during protein adsorption. We show that, at the
end of protein adsorption process, the system sustains a residual local tension
to balance the difference between the actual mean curvature and the imposed
spontaneous curvatures. This change in membrane tension can have a functional
impact in many biological phenomena where proteins interact with membranes.Comment: 15 pages, 5 figure
Recommended from our members
Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium.
Dendritic spines are small subcompartments that protrude from the dendrites of neurons and are important for signaling activity and synaptic communication. These subcompartments have been characterized to have different shapes. While it is known that these shapes are associated with spine function, the specific nature of these shape-function relationships is not well understood. In this work, we systematically investigated the relationship between the shape and size of both the spine head and spine apparatus, a specialized endoplasmic reticulum compartment within the spine head, in modulating rapid calcium dynamics using mathematical modeling. We developed a spatial multicompartment reaction-diffusion model of calcium dynamics in three dimensions with various flux sources, including N-methyl-D-aspartate receptors (NMDARs), voltage-sensitive calcium channels (VSCCs), and different ion pumps on the plasma membrane. Using this model, we make several important predictions. First, the volume to surface area ratio of the spine regulates calcium dynamics. Second, membrane fluxes impact calcium dynamics temporally and spatially in a nonlinear fashion. Finally, the spine apparatus can act as a physical buffer for calcium by acting as a sink and rescaling the calcium concentration. These predictions set the stage for future experimental investigations of calcium dynamics in dendritic spines
Recommended from our members
A predictive computational model reveals that GIV/girdin serves as a tunable valve for EGFR-stimulated cyclic AMP signals.
Cellular levels of the versatile second messenger cyclic (c)AMP are regulated by the antagonistic actions of the canonical G protein → adenylyl cyclase pathway that is initiated by G-protein-coupled receptors (GPCRs) and attenuated by phosphodiesterases (PDEs). Dysregulated cAMP signaling drives many diseases; for example, its low levels facilitate numerous sinister properties of cancer cells. Recently, an alternative paradigm for cAMP signaling has emerged in which growth factor-receptor tyrosine kinases (RTKs; e.g., EGFR) access and modulate G proteins via a cytosolic guanine-nucleotide exchange modulator (GEM), GIV/girdin; dysregulation of this pathway is frequently encountered in cancers. In this study, we present a network-based compartmental model for the paradigm of GEM-facilitated cross-talk between RTKs and G proteins and how that impacts cellular cAMP. Our model predicts that cross-talk between GIV, Gαs, and Gαi proteins dampens ligand-stimulated cAMP dynamics. This prediction was experimentally verified by measuring cAMP levels in cells under different conditions. We further predict that the direct proportionality of cAMP concentration as a function of receptor number and the inverse proportionality of cAMP concentration as a function of PDE concentration are both altered by GIV levels. Taking these results together, our model reveals that GIV acts as a tunable control valve that regulates cAMP flux after growth factor stimulation. For a given stimulus, when GIV levels are high, cAMP levels are low, and vice versa. In doing so, GIV modulates cAMP via mechanisms distinct from the two most often targeted classes of cAMP modulators, GPCRs and PDEs
- …