Curvature-Modulated Phase Separation in Lipid Bilayer Membranes

Abstract

Cellular membranes exhibit a variety of controlled curvatures, with filopodia, microvilli, and mitotic cleavage furrows being only a few of many examples. Coupling between local curvature and chemical composition in membranes could provide a means of mechanically controlling the spatial organization of membrane components. Although this concept has surfaced repeatedly over the years, controlled experimental investigations have proven elusive. Here, we introduce an experimental platform, in which microfabricated surfaces impose specific curvature patterns onto lipid bilayers, that allows quantification of mechanochemical couplings in membranes. We find that, beyond a critical curvature value, membrane geometry governs the spatial ordering of phase-separated domain structures in membranes composed of cholesterol and phospholipids. The curvature-controlled ordering, a consequence of the distinct mechanical properties of the lipid phases, makes possible a determination of the bending rigidity difference between cholesterol-rich and cholesterol-poor lipid domains. These observations point to a strong coupling between mechanical bending and chemical organization that should have wide-reaching consequences for biological membranes. Curvature-mediated patterning may also be useful in controlling complex fluids other than biomembranes.

Specific adhesion of membranes simultaneously supports dual heterogeneities in lipids and proteins

“…Other researchers have examined the role of membrane curvature in the segregation of pre-existing phases. 14,30,31 They found that stiffer, ordered-phase domains segregate to regions of lower curvature. This minimizes the net bending energy of the system.…”

Lipid-Mediated Endocytosis

“…Such deformation helps to reduce the length of the phase boundary, and thus the energy of line tension (Baumgart et al 2003). Once the membrane is deformed, the induction of curvature by the bound virus and AB5 toxin can further enhance phase separation, which may act as a feedback loop (Parthasarathy et al 2006).…”

Glycans pattern the phase behaviour of lipid membranes

“…It is clear from the images, the PSDs, the cross-correlation analysis, and the intensity contour plots that the replica does not pattern the phase separation of the membrane. It might be possible that there are differences at the nanoscale regarding the contours of the lipid bilayers and the substrates, but it is unlikely to be a main factor given the many papers that report lipid bilayers follow faithfully the topography of even highly rough silica substrates [15][16][17] . We thus conclude that the gross topography of the glycan network alone cannot pattern domains in multiphase membranes.…”

“…Indeed, while there are many reports of lipid membranes supported on non-biological polymers such as polyethylene glycol, polyacrylamide or polyethyleneimine [17][18][19][20] which seek to mitigate non-'equilibrium' behaviour, such systems have been used mainly to study the effects of polymer hydration 21 on the mobility of lipids 18,19 , or to preserve the function of transmembrane protein inclusions 17,22 . Furthermore, while it is widely acknowledged that a greater understanding of parameters that influence the size and length-scale of membrane domains is required [6][7][8][9][10][11][12][13]23,24 , as far as we know, systematic studies exploring the effects of biopolymers (the subject of this letter), or other more commonly used polymers in the field [17][18][19][20] on the phase behaviour of lipid membranes have not been conducted. To investigate the possible effects of biologically relevant polymers on the behaviour of membranes, we designed an in vitro solid-supported experimental platform that allows, through fluorescent labelling and confocal microscopy, the study of lipid membranes interacting with hydrated networks of glycans with arbitrary glycan composition and variable network configurations.…”