Computation of Lipid Headgroup Interactions

The equilibrium structure of lipid aggregates is determined by the balance of numerous forces between hydrophobic acyl chains, hydrophilic lipid headgroups, and the lipid\u27s environment. Among these forces, lipid headgroup interactions are both important to the stability of lipid structures and responsible for many of the interactions between biological membranes and aqueous solutes including ions and soluble peptides. In order to model these headgroup interactions, we consider the electrical properties of the headgroup molecules via the multipole expansion. While common lipid headgroups such as phosphatidylcholine are electrically neutral, they are characterized by non-zero higher order terms in the multipole expansion. Making a dipole approximation, we employ a two dimensional lattice of classical dipoles to model the headgroup networks of lipid aggregates. Restrictions to each dipole\u27s position and orientation are imposed to account for the effect of hydrocarbon chains which are not included in the model. A Monte Carlo algorithm is used to calculate headgroup-headgroup interactions and network energies in both dipole and point-charge approximations

Collaborative Research from the Center for Membrane Biosciences

poster abstractThe Center for Membrane Biosciences has been facilitating new research activities between the IUPUI School of Science and IU School of Medicine in the structure, biochemistry, and physiology of biological membranes. Results from two projects resulting from these collaborations are presented. Project 1: Ceramides are sphingolipids involved in the development of lung alveolar cell apoptosis (programmed death) and possibly in the clearance of apoptotic cells by alveolar macrophages. We use a combination of molecular and cellular methods to determine the effect of ceramides on the ability of alveolar macrophages to engulf apoptotic cells. Engulfment experiments of labeled apoptotic Jurkat cells were performed with rat alveolar macrophages (AM) obtained via bronchoalveolar lavage. AM were treated with various ceramide species and efferocytosis was quantified by flow cytometry. Using small-angle X-ray scattering and solid state 2H NMR we determined how ceramides (C6:0, C18:1) affect the molecular organization and the physical properties of model membranes. These studies can lead to a better understanding of the molecular mechanisms responsible for apoptotic cell clearance. If the clearance process is impaired, apoptotic cells may progress to secondary necrosis, resulting in release of harmful cellular contents and tissue inflammation. Project 2: Highly-photostable quantum dots (QD) conjugated to lipids or antibodies can be utilized to explore changes in compartmentalization of the plasma membrane due to hyperinsulinemia using wide field single molecule fluorescence microscopy. Protocols describing the bio-inertness and monovalent binding of QDs to antibodies are outlined, as well as use of confocal fluorescence correlation spectroscopy to determine colloidal stability of CdSe/ZnS QDs in aqueous solution. Tracking experiments on QD-conjugated to transferrin receptors in healthy and insulin-resistant adipocytes detect changes in membrane compartmentalization. The impact of chromium picolinate on receptor mobility was also investigated

ADMISSION TO THE PSYCHIATRIC EMERGENCY SERVICES OF PATIENTS WITH ALCOHOL-RELATED MENTAL DISORDER

Abstract

Medical Rapid Response in Psychiatry: Reasons for Activation and Immediate Outcome

Rapid response teams are used to improve the recognition of acute deteriorations in medical and surgical settings. They are activated by abnormal physiological parameters, symptoms or clinical concern, and are believed to decrease hospital mortality rates. We evaluated the reasons for activation and the outcome of rapid response interventions in a 222-bed psychiatric hospital in New York City using data obtained at the time of all activations from January through November, 2012. The primary outcome was the admission rate to a medical or surgical unit for each of the main reasons for activation. The 169 activations were initiated by nursing staff (78.7 %) and psychiatrists (13 %) for acute changes in condition (64.5 %), abnormal physiological parameters (27.2 %) and non-specified concern (8.3 %). The most common reasons for activation were chest pain (14.2 %), fluctuating level of consciousness (9.5 %), hypertension (9.5 %), syncope or fall (8.9 %), hypotension (8.3 %), dyspnea (7.7 %) and seizures (5.9 %). The rapid response team transferred 127 (75.2 %) patients to the Emergency Department and 46 (27.2 %) were admitted to a medical or surgical unit. The admission rates were statistically similar for acute changes in condition, abnormal physiological parameters, and clinicians\u27 concern. In conclusion, a majority of rapid response activations in a self-standing psychiatric hospital were initiated by nursing staff for changes in condition, rather than for policy-specified abnormal physiological parameters. The findings suggest that a rapid response system may empower psychiatric nurses to use their clinical skills to identify patients requiring urgent transfer to a general hospital

Effects of Lipid Interactions on Model Vesicle Engulfment by Alveolar Macrophages

The engulfment function of macrophages relies on complex molecular interactions involving both lipids and proteins. In particular, the clearance of apoptotic bodies (efferocytosis) is enabled by externalization on the cell target of phosphatidylserine lipids, which activate receptors on macrophages, suggesting that (local) specific lipid-protein interactions are required at least for the initiation of efferocytosis. However, in addition to apoptotic cells, macrophages can engulf foreign bodies that vary substantially in size from a few nanometers to microns, suggesting that nonspecific interactions over a wide range of length scales could be relevant. Here, we use model lipid membranes (made of phosphatidylcholine, phosphatidylserine, and ceramide) and rat alveolar macrophages to show how lipid bilayer properties probed by small-angle x-ray scattering and solid-state 2H NMR correlate with engulfment rates measured by flow cytometry. We find that engulfment of protein-free model lipid vesicles is promoted by the presence of phosphatidylserine lipids but inhibited by ceramide, in accord with a previous study of apoptotic cells. We conclude that the roles of phosphatidylserine and ceramide in phagocytosis is based, at least in part, on lipid-mediated modification of membrane physical properties, including interactions at large length scales as well as local lipid ordering and possible domain formation