High Transmembrane Voltage Raised by Close Contact Initiates Fusion Pore

Abstract

Membrane fusion lies at the heart of neuronal communication but the detailed mechanism of a critical step, fusion pore initiation, remains poorly understood. Here, through atomistic molecular dynamics simulations, a transient pore formation induced by a close contact of two apposed bilayers is firstly reported. Such a close contact gives rise to a high local transmembrane voltage that induces the transient pore formation. Through simulations on two apposed bilayers fixed at a series of given distances, the process in which two bilayers approaching to each other under the pulling force from fusion proteins for membrane fusion was mimicked. Of note, this close contact induced fusion pore formation is contrasted with previous reported electroporation under ad hoc applied external electric field or ionic charge in-balance. We show that the transmembrane voltage increases with the decrease of the distance between the bilayers. Below a critical distance, depending on the lipid composition, the local transmembrane voltage can be sufficiently high to induce the transient pores. The size of these pores is approximately 1~2 nm in diameter, which is large enough to allow passing of neurotransmitters. A resealing of the membrane pores resulting from the neutralization of the transmembrane voltage by ions through the pores was then observed. We also found that the membrane tension can either prolong the lifetime of transient pores or cause them to dilate for full collapse. This result provides a possible mechanism for fusion pore formation and regulation of pathway of fusion process.

Membrane Fusion Involved in Neurotransmission: Glimpse from Electron Microscope and Molecular Simulation

“…CG MD simulation is one of effective solutions to overcome the time-scale gap between computational and experimental methods (Bhushan, 2016 ). With the aid of residue-based and shape-based CG approaches, the regulatory mechanisms of SNARE proteins have been briefly outlined, focused on the intricate molecular mechanisms between proteins and membranes (Bu et al, 2016 ; Zhang et al, 2016 ; Han et al, 2017 ). However, the application of CG models sacrifice degrees of freedom and accurate molecular interactions to get the requirement of less resources (Bhushan, 2016 ).…”

“…The decrease of the distance of the opposed bilayers brings out the increase of the transmembrane voltage. When the distance is under a critical value, the local transmembrane voltage is enough high to induce the transient of membrane pores (Figure 4 ; Ribrault et al, 2011 ; Bu et al, 2016 ). Finally, some findings have offered new structural and dynamic details of SNARE disassembly mechanism based on CG modeling (Zheng, 2016 ).…”

“… Snapshots and electrical potential distributions during the process of fusion pore (membrane contact-pore formation-membrane healing) through the molecular dynamics (MD) simulations (A–C) : the process of fusion pore formation. (D–F) : electric potential alteration during the process (Bu et al, 2016 ). …”

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“…Membrane fusion can be regulated by the physicochemical property of the lipids and the structure of SNAREs (1,(11)(12)(13)(14)(15)(16). For instance, Katsov et al (11) investigated how lipid compositions influences fusion process, suggesting that lipids with spontaneous negative curvature (e.g.…”

The biological effect of 2.45 GHz microwaves on the viability and permeability of bacterial and yeast cells

“…proteins and lipids) which change their behaviour in the presence of an E field (9,10). In the case of membrane phospholipids, when voltage drop associated with the applied E field is greater than the membrane potential, the lipids reorient to the E field, resulting in membrane destabilisation and the formation of transient gaps (pores) (11,12). The effective transmembrane potential required to induce membrane poration is between 0.2-1.0 V (13,14).…”