Biological & Soft Matter Seminar: Focusing on Phosphatidyl Serine: from structural studies at the air-water interface to asymmetric bilayer model systems

Abstract:

Cell membranes are characterized by complex lipid composition and organization. Of particular interest is the asymmetric distribution of phospholipids such as phosphatidyl serine (PS) across the membrane and how this asymmetry, as well as its loss as a result of cell activation, couples to the lateral organization of lipids in cell membranes. PS is involved in several intra‐ and inter‐cellular signaling cascades that are paramount to the functioning of multicellular organisms. Their examples include apoptosis and blood coagulation, where the expression of PS on the outer cell surface serves as a signal for the clearance of apoptotic cells and a site for the assembly of coagulation factors, respectively; cell membrane repair, where PS serves as a site of adhesion for annexin A5 that functions as a band aid; immune regulation; fusion of secretory vesicles with cell membranes; anchoring of the cytoskeleton; and regulation of signal‐mediated kinase activity inside the cells. Many of these activities involve interaction of PS with calcium. Despite these numerous and crucial roles, the structure of phosphatidyl serines is relatively poorly investigated (e.g., in comparison with the other lipids), and their interaction with calcium is not very well understood. We conducted neutron and X‐ray reflectometry studies at the air‐water interface to investigate structural properties of Ca‐bound and Ca‐free forms of unsaturated PS lipids. Evidence of conformational change upon calcium binding, predicted from the early spectroscopic studies of Ca localization in the PS headgroup, is apparent in our data.

Model systems to study asymmetric membrane systems are scarce. We developed a model system that captures both the compositional complexity of the cell membranes and the asymmetric distribution of the lipids in them. The system is based on supported lipid bilayers (SLBs) on TiO2. They contain the canonical high‐melting, low‐melting, cholesterol lipid mixture commonly used to model cell membranes, plus phosphatidyl serine (PS), which strongly interacts with TiO2 and is therefore distributed asymmetrically. The strong PS‐TiO2 interaction mimics the cytoskeleton‐cell membrane interactions that occur in the cell. These SLBs were characterized using a range of techniques, including neutron reflectometry, to ascertain their composition, lateral and transverse organization, and melting behavior. Further, the membranes on TiO2 were compared with SiO2 membranes of nominally identical composition. We therefore have well‐characterized membrane‐mimetic systems that could be used to study membrane dynamics.

Seminar Organizer: Guy Yaacoby