The dipole potential of a lipid bilayer membrane accounts for its much larger permeability to anions than cations and affects the conformation and function of membrane proteins. The absolute value of the dipole potential has been very difficult to measure, although its value has been estimated to range from 200 to 1,000 mV from ion translocation rates, the surface potential of lipid monolayers, and molecular dynamics calculations. Here, a point charge probe method was used to investigate the dipole potentials of both ester and ether lipid membranes. The interactions between electrons and lipid molecules were recorded by phase-contrast imaging using cryo-EM. The magnitude and the profile of the dipole potential along the bilayer normal were obtained by subtracting the contribution of the atomic potential from the cryo-EM image intensity. The peak dipole potential was estimated to be 510 and 260 mV for diphytanoylphosphatidylcholine and diphytanylphosphatidylcholine, respectively.liposome ͉ phospholipid ͉ atomic potential ͉ electron-phase shift ͉ molecular dynamics N egatively charged molecules diffuse across phospholipid membranes with great ease when compared with positively charged ones (1). For example, the tetraphenylborate anion (TPB Ϫ ) has a permeability Ϸ3 ϫ 10 7 larger than the identically sized tetraphenylarsonium cation (TPA ϩ ) in membranes formed from the neutral lipid phosphatidylcholine (2). A remarkably large positive electrostatic potential in the interior of the membrane accounts for much of this permeability difference. The size of this potential is influenced little by the charge or nature of the polar headgroups, but is thought mainly to arise from the dipole moment of the ester linkage of the hydrocarbon chains ( Fig. 1) (3). Beside the translocation rates of ions across lipid membranes, this dipole potential affects the structure and function of membrane-incorporated proteins such as a model amphiphilic peptide (4), gramicidin A (5, 6), and phospholipase A (7). It has also been suggested that the dipole potential may play a role in the function and conformation of proteins in lipid rafts, where the dipole potential is different from surrounding lipids because of associated sterols within the raft structure (8).The absolute value of the dipole potential has been very difficult to measure or predict, and estimates obtained from various methods range from ϩ200 to ϩ1,000 mV (Table 1). One experimental method, the bilayer method, relies on the assumption that the thermodynamic properties of TPA ϩ and TPB Ϫ are identical, except for their charges. In this case the ratio of permeabilities directly yields an estimate of Ϸ230 mV for the peak dipole potential in a phosphatidylcholine membrane. A relaxation of the assumption of identical properties (9, 10), in particular taking into account the smaller hydration energy of TPB Ϫ (11) yields estimates for the dipole potential that are Ϸ100 mV larger (Table 1, Bilayer ϩ ⌬G hydr values).In the lipid monolayer method, an ''air electrode'' is used to measur...

Influenza A virus interacts with specific types of sialic acid during attachment and entry into susceptible cells. The precise amino acids in the hemagglutinin protein that control sialic acid binding specificity and affinity vary among antigenic subtypes. For H3 subtypes, amino acids 226 and 228 are critical for differentiating between α2,3- and α2,6-linked forms of sialic acid (SA). We demonstrate that position 190 of the HA from A/Udorn/307/72 (H3N2) plays an important role in the recognition of α2,3-SA, as changing the residue from a glutamic acid to an aspartic acid led to alteration of red blood cell hemagglutination and a complete loss of replication in differentiated, murine trachea epithelial cell cultures which express only α2,3-SA. This amino acid change had a minimal effect on virus replication in MDCK cells, suggesting subtle changes in receptor recognition by the H3 hemagglutinin can lead to significant alterations in cell and species tropism.

Figure 2 Diagnostic and therapeutic paracentesis yielded 2.4 liters of milky ascites.

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