Elucidating mysteries of phase-segregated membranes: mobile-lipid recruitment facilitates pores’ passage to the fluid phase

Abstract

Phase segregation of multicomponent lipid bilayers leads to, under phase-coexistence conditions, domain formation, featuring delimitation by essentially one-dimensional borders. (Micro-)phase segregation of bilayers is proposed to influence the physiological behaviour of cell membranes and provides the driving force for lipid-raft formation. Experiments show a maximum in the electrical-conductivity of membranes at the phase-transition point, which has been conjectured to arise from border-nucleated transmembrane-conducting defects or pores. However, recent electroporation experiments on phase-segregated bilayers demonstrate electro-pore detection in the liquid disordered phase (L_d), wherein they diffuse over macroscopic periods without absorption into the liquid ordered phase (L_o). Here, we scrutinise transmembrane-pore formation via molecular dynamics simulations on a multicomponent phase-segregated bilayer. We find that pores created in L_o domains always migrate spontaneously to the L_d phase, via ‘recruitment’ of unsaturated lipids to the pore's rim to transport the pore to the fluid phase under a large stress-field driving force. Once in L_d domains, pores migrate towards their centre, never returning or pinning to L_o. These findings are explained by thermodynamics. By comparing the free-energy cost for creating pores in the bulk of L_d and L_o membranes, and in the phase-segregated system, we show that it is always more energetically tractable to create pores in L_d domains, independent of the pore size.