PMC

Molecular geometry of lipids and membrane stored stress. Monolayers made of cylindrical molecules of zero SC can form nonstressed lamellas (first column, green lipid). However, for nonzero SC, lipid molecules have to be reshaped to fit into a flat state, leading to membrane stress (second column, orange lipid). When the packing parameter of the lipid is too far from unity, the stress accumulated in the resulting bilayer is too big; hence the transition of the lamella into a nonlamellar (e.g., H_II) phase is favorable. The transition begins when small interlammellar contacts having characteristic hourglass shape form (third column, red lipid), lipids with negative SC promotes formation of these localized nonbilayer structures.

Phase diagram of the tubules. The y axis represents the mole fraction of the nonbilayer lipid and the x axis represents , where Δζ is the difference between the spontaneous curvature of this lipid and that of the background. Region I corresponds to the smooth cylindrical shape. Region II corresponds to the pearled shape. The numerically computed phase boundary is indicated by the solid line. The vertical lines represent (a) a lipid unable to induce pearling, and (b) a lipid capable of pearling the tubule.

Schematic diagram of tBid- and chymBid-induced LMP. During the initiation phase of LMP, tBid formed by activated caspase 8 is targeted to the lysosomal membranes by interaction with PA, where tBid changes conformation, forms homo-oligomers, and triggers the formation of nonbilayer lipid phases, which account for the formation of “lipidic pores” and the consequent initiation of LMP. As a result of LMP, different lysosomal proteases are redistributed into the cytosol, among them chymotrypsin, which rapidly cleaves Bid to form chymBid. chymBid shows stronger interaction with PA, triggers the formation of more nonbilayer lipid phases, and causes more significant LMP. This amplification of LMP culminates in the lysosome-dependent apoptotic signaling.

How bilayer pressure can shape membrane proteins or cause the bilayer to adapt to them. (a) Nonbilayer lipids can make an hourglass shape more stable. (b) The drive to shield hydrophobic side chains can either alter the protein conformation, the bilayer conformation, or both. Lipid shapes can facilitate or hinder bilayer adjustments