PT - JOURNAL ARTICLE AU - M. Pinot AU - S. Vanni AU - E. Ambroggio AU - D. Guet AU - B. Goud AU - J.-B. Manneville TI - Feedback between membrane tension, lipid shape and curvature in the formation of packing defects AID - 10.1101/389627 DP - 2018 Jan 01 TA - bioRxiv PG - 389627 4099 - http://biorxiv.org/content/early/2018/08/13/389627.short 4100 - http://biorxiv.org/content/early/2018/08/13/389627.full AB - Lipid packing defects favor the binding of proteins to cellular membranes by creating spaces between lipid head groups that allow the insertion of amphipathic helices or lipid modifications. The density of packing defects in a lipid membrane is well known to increase with membrane curvature and in the presence of conical-shaped lipids. In contrast, the role of membrane tension in the formation of lipid packing defects has been poorly investigated. Here we use a combination of numerical simulations and experiments to measure the effect of membrane tension on the density of lipid packing defects. We first monitor the binding of ALPS (amphipathic lipid packing sensor) to giant unilamellar vesicles and observe a striking periodic binding of ALPS that we attribute to osmotically-induced membrane tension and transient membrane pore formation. Using micropipette aspiration experiments, we show that a high membrane tension induces a reversible increase in the density of lipid packing defects. We next focus on packing defects induced by lipid shape and show that conical lipids generate packing defects similar to that induced by membrane tension and enhance membrane deformation due to the insertion of the ALPS helix. Both cyclic ALPS binding and the cooperative effect of ALPS binding and conical lipids on membrane deformation result from an interplay between helix insertion and lipid packing defects created by membrane tension, conical lipids and/or membrane curvature. We propose that feedback mechanisms involving membrane tension, lipid shape and membrane curvature play a crucial role in membrane deformation and intracellular transport events.