Publications by authors named "Zachary Graber"

Lipid bilayer membranes undergo rapid bending undulations with wavelengths from tens of nanometers to tens of microns due to thermal fluctuations. Here, we probe such undulations and the membranes' mechanics by measuring the time-varying orientation of single gold nanorods (GNRs) adhered to the membrane, using high-speed dark field microscopy. In a lipid vesicle, such measurements allow the determination of the membrane's viscosity, bending rigidity, and tension as well as the friction coefficient for sliding of the monolayers over one another.

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Diacylglycerol pyrophosphate (DGPP) is an anionic phospholipid formed in plants, yeast, and parasites under multiple stress stimuli. It is synthesized by the phosphorylation action of phosphatidic acid (PA) kinase on phosphatidic acid, a signaling lipid with multifunctional properties. PA functions in the membrane through the interaction of its negatively charged phosphomonoester headgroup with positively charged proteins and ions.

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Cells respond to both physical and chemical aspects of their substrate. Whether intracellular signals initiated by physical stimuli are fundamentally different from those elicited by chemical stimuli is an open question. Here, we show that the requirement for a stiff substrate (and, therefore, high cellular tension) for cells to produce large focal adhesions and stress fibers is obviated when a soft substrate contains both hyaluronic acid (HA) and an integrin ligand (collagen I).

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The fluid-mosaic model posits a liquid-like plasma membrane, which can flow in response to tension gradients. It is widely assumed that membrane flow transmits local changes in membrane tension across the cell in milliseconds, mediating long-range signaling. Here, we show that propagation of membrane tension occurs quickly in cell-attached blebs but is largely suppressed in intact cells.

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Lamellar to nonlamellar membrane shape transitions play essential roles in key cellular processes, such as membrane fusion and fission, and occur in response to external stimuli, including drug treatment and heat. A subset of these transitions can be modeled by means of thermally inducible amphiphile assemblies. We previously reported on mixtures of hydrogenated, fluorinated, and hybrid Janus dendrimers (JDs) that self-assemble into complex dendrimersomes (DMSs), including dumbbells, and serve as promising models for understanding the complexity of biological membranes.

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The phosphoinositide, phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P), is a key signaling lipid in the inner leaflet of the cell plasma membrane, regulating diverse signaling pathways including cell growth and migration. In this study we investigate the impact of the hydrogen-bond donor lipids phosphatidylethanolamine (PE) and phosphatidylinositol (PI) on the charge and phase behavior of PI(3,4,5)P. PE and PI can interact with PI(3,4,5)P through hydrogen-bond formation, leading to altered ionization behavior and charge distribution within the PI(3,4,5)P headgroup.

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Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) is an important signaling lipid and plays a crucial role in a wide variety of cellular processes by interacting with protein targets and localizing proteins at the plasma membrane. These interactions are strongly influenced by the lateral distribution of PI(4,5)P2 as well as its ionization state. The characterization of the PI(4,5)P2 ionization state provides important information about how PI(4,5)P2 interacts with other membrane resident or associated chemical species.

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Detailed knowledge of the degree of ionization of lipid titratable groups is important for the evaluation of protein-lipid and lipid-lipid interactions. The degree of ionization is commonly evaluated by acid-base titration, but for lipids localized in a multicomponent membrane interface this is not a suitable technique. For phosphomonoester-containing lipids such as the polyphosphoinositides, phosphatidic acid, and ceramide-1-phosphate, this is more conveniently accomplished by (31)P NMR.

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Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) is an important lipidic signaling molecule that is involved in a broad range of cellular processes. Its interaction with proteins and its lateral distribution are governed by the ionization state of the phosphomonoester groups and its ability to form intra- and intermolecular hydrogen bonds. In this study we have investigated the ionization state of PI(4,5)P(2) in ternary lipid vesicle systems that contain in addition to PI(4,5)P(2) and phosphatidylcholine (PC) either phosphatidylethanolamine (PE), phosphatidylserine (PS) or phosphatidylinositol (PI).

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