Long and Short Lipid Molecules Experience the Same Interleaflet Drag in Lipid Bilayers

Abstract

Membrane interleaflet viscosity η e affects tether formation, phase separation into domains, cell shape changes, and budding. Contrary to the expected contribution to interleaflet coupling from interdigitation, the slide of lipid patches in opposing monolayers conferred the same value η e ≈ 3×10 9 J s m −4 for the friction experienced by the ends of both short and long chain fluorescent lipid analogues. Consistent with the weak dependence of the translational diffusion coefficient on lipid length, the in-layer viscosity was, albeit length dependent, much smaller than η e .The ability of the two membrane leaflets to slide against each other is of utmost importance for manifold cellular processes like (i) filopodia formation in cell migration [1], (ii) tether formation for neutrophil attachment to platelets during inflammation or thrombosis [2], (iii) membrane fusion [3], or (iv) membrane budding and fission [4]. In order for signaling platforms, so-called rafts to emerge, sterol and sphingolipid enriched domains must align in the two membrane monolayers [5]. Experiments on lipid bilayers suggest that such alignment is stabilized by a yet unidentified coupling mechanism. For example, lipid mixture in one leaflet of asymmetric lipid bilayers may induce the formation of registered clusters on the other leaflet, though it contains lipids which would not phase separate in a symmetric bilayer [6]. Finally, lipid interactions at the membrane midplane seem to have an impact on the mobility of individual lipid molecules [7].What actually determines how tightly the leaflets are coupled to each other or how easily they slide against each other is under debate [6,[8][9][10]. For example, minimization of energy expenses on local curvature [11] or maximization of the free undulation energy [12] have been put forward to explain registration of ligand-induced lipid spots of higher chain orientational order in the two leaflets. Gelation of both leaflets upon binding of negatively charged particles to only one monolayer of initially homogenous fluid lipid bilayers [13] may reflect a decreased capacity of one leaflet to accommodate disorder due to bindinginduced local stiffening of the other leaflet.

Undulations Drive Domain Registration from the Two Membrane Leaflets

“…Thus, domains in the substrate-adhering leaflet are completely immobile laterally. Domain movement in the opposing leaflet must also be hampered because of the strong friction between the monolayers (13). In consequence domain motion is completely missing in the nonadhering leaflet of supported planar bilayers that were created by the Langmuir-Blodgett technique (30).…”

“…Most prevalent is the idea that the two leaflets interact at the membrane midplane via overhang. However, measurements of interleaflet friction revealed the same mobility for long and short lipid molecules suggesting that there might not be permanent overhang (13). Nevertheless, the hypothesis about membrane midplane interaction is still en vogue, although, it is unclear 1) whether the liquid-disordered (L d ) domains and L o domains repel each other, or 2) whether the phenomenon is caused by attraction of the two L d domains and/or the two L o domains, or 3) what the underlying attractive or repulsive forces may generate (14,15).…”

Shape matters in protein mobility within membranes

“…One can evaluate the relative importance of these contributions in Eq. 5 using the following bilayer parameters a = 5 nm, d = 1 nm (19), b = 10 9 J·s·m −4 (20)(21)(22) and μ m = 6 × 10 −10 J·s·m −2 (23), from which one finds the dimensionless factors bd 2 =ηa ' 200, ðd=aÞ 2 ' 0:04, and μ m d 2 =2ηa 3 ' 2. It follows from such estimates that the monolayer friction should play the largest role in the effective friction of the protein (Eq.…”

Elastic Membrane Deformations Govern Interleaflet Coupling of Lipid-Ordered Domains

“…Since neither multivalent ligand binding to membranes, nor leaflet composition are symmetric, coupled phase separation in both monolayers was thought to be due to interlayer friction [22,23]. This idea seems questionable, since friction of the opposing leaflets cannot keep domains in register, even if the interlayer friction is tenfold larger than the in-layer friction [24]. The alternative idea is that stiff regions in both monolayers attract each other because their registration minimizes spatial restrains on membrane undulations (i.e., registration maximizes entropy [20]).…”