(717e) Floret-Shaped Solid Domains On Fluid Lipid Vesicles Induced by pH

Heterogeneous lipid bilayers containing lipid ordered domains are studied due to their potential relevance to critical biological phenomena including membrane trafficking, protein transport and viral infection mechanisms.  Studies, however, on heterogeneous lipid membranes with gel-fluid coexisting regions are limited despite their importance to micropatterning of spherical particles relevant to photonic crystals and their potential in medical applications.  We are particularly interested in the potential role of gel-fluid heterogeneities on altering collective membrane properties such as surface topography and functionality, membrane permeability and/or fusogenicity. These lipid membranes in the form of small lipid vesicles can be ultimately applied as drug delivery carriers for cancer therapy. We focus on the environmentally responsive formation of gel-fluid heterogeneities on lipid bilayers using pH-dependent processes on model lipid membranes in the form of Giant Unilamellar Vesicles (GUVs). 

Fluorescence microscopy reveals that lowering pH (from 7.0 to 5.0) controls the condensation of phase-separating domains on fluid GUVs resulting in beautiful floret-shaped solid formations rich in phosphatidylserine or phosphatidic acid lipids tightly packed via H-bonding and VdWs interactions. Solid domains comprise a circular “core” cap beyond which interfacial instabilities emerge resulting in leaf-like structures of almost vanishing Gaussian curvature independent of GUVs’ preparation path and in agreement with a general kinetic mechanism. Increasing incompressibility of domains is strongly correlated with larger numbers of leaves, and increasing relative rigidity of domains with smaller core cap areas. Line tension drives domain ripening, however the final domain shape is a result of enhanced incompressibility and rigidity determined by domain coupling across the bilayer. The domain condensation process is frustrated by the buildup of osmotic pressure within GUVs and proceeds further upon inversion or decrease of the transbilayer osmotic gradient.