Needle Size and Injection Rate Impact Microbubble Contrast Agent Population

The most common type of ultrasound contrast agents are encapsulated microbubbles, typically 1–5 microns in diameter. These microbubbles are injected into the bloodstream to provide image enhancement during an ultrasound exam. Due to their compressibility, these microbubbles are inherently sensitive to changes in pressure. For imaging, this is beneficial in that these microbubbles oscillate in an acoustic field and allow imaging systems to detect their response uniquely from tissue. However, this sensitivity also means that microbubbles can be readily destroyed by significant hydrostatic pressure. Injection of these microbubbles through a small-gauge catheter, such as sometimes performed in small animal imaging studies, can result in microbubble destruction. In this manuscript, the effects of microbubble injection through catheters of varying diameter are examined. Our results indicate that the concentration and size distribution of microbubbles can be substantially altered in cases of rapid injection through small needles

Modeling Amyloid Beta Peptide Insertion into Lipid Bilayers

Inspired by recent suggestions that the Alzheimer's amyloid beta peptide (A beta) can insert into cell membranes and form harmful ion channels, we model insertion of the 40 and 42 residue forms of the peptide into cell membranes using a Monte Carlo code which is specific at the amino acid level. We examine insertion of the regular A-beta peptide as well as mutants causing familial Alzheimer's disease, and find that all but one of the mutants change the insertion behavior by causing the peptide to spend more simulation steps in only one leaflet of the bilayer. We also find that A-beta 42, because of the extra hydrophobic residues relative to A-beta 40, is more likely to adopt this conformation than A-beta 40 in both wild-type and mutant forms. We argue qualitatively why these effects happen. Here, we present our results and develop the hypothesis that this partial insertion increases the probability of harmful channel formation. This hypothesis can partly explain why these mutations are neurotoxic simply due to peptide insertion behavior. We further apply this model to various artificial A-beta mutants which have been examined experimentally, and offer testable experimental predictions contrasting the roles of aggregation and insertion with regard to toxicity of A-beta mutants. These can be used through further experiments to test our hypothesis.Comment: 14 pages; 8 figures; 2nd revisio

Biophysical properties of membrane lipids of anammox bacteria:I. Ladderane phospholipids form highly organized fluid membranes

AbstractAnammox bacteria that are capable of anaerobically oxidizing ammonium (anammox) with nitrite to nitrogen gas produce unique membrane phospholipids that comprise hydrocarbon chains with three or five linearly condensed cyclobutane rings. To gain insight into the biophysical properties of these ‘ladderane’ lipids, we have isolated a ladderane phosphatidylcholine and a mixed ladderane phosphatidylethanolamine/phosphatidylglycerol lipid fraction and reconstituted these lipids in different membrane environments. Langmuir monolayer experiments demonstrated that the purified ladderane phospholipids form fluid films with a relatively high lipid packing density. Fluid-like behavior was also observed for ladderane lipids in bilayer systems as monitored by cryo-electron microscopy on large unilamellar vesicles (LUVs) and epi-fluorescence microscopy on giant unilamellar vesicles (GUVs). Analysis of the LUVs by fluorescence depolarization revealed a relatively high acyl chain ordering in the hydrophobic region of the ladderane phospholipids. Micropipette aspiration experiments were applied to study the mechanical properties of ladderane containing lipid bilayers and showed a relatively high apparent area compressibility modulus for ladderane containing GUVs, thereby confirming the fluid and acyl chain ordered characteristics of these lipids. The biophysical findings in this study support the previous postulation that dense membranes in anammox cells protect these microbes against the highly toxic and volatile anammox metabolites