Stuart McLaughlin

Bio: Stuart McLaughlin is an academic researcher from Stony Brook University. The author has contributed to research in topics: Membrane & Lipid bilayer. The author has an hindex of 61, co-authored 87 publications receiving 13501 citations. Previous affiliations of Stuart McLaughlin include State University of New York System & National University of Singapore.

The electrostatic properties of membranes.

Abstract: CONTENTS PERSPECTIVES AND OVERVlEW . . . . . . . . . . . . ...... . . . . . . . . . . . . . . ...... . . . . . . . . . . . . . . . . . .. . . . . . . . . . ....... . . . . . . . . . . . . ... 113 AN ELEMENTARY DISCUSSION OF ELECTROSTATICS AND DOUBLE-LAYER THEORy 115 EXPERIMENTAL TESTS OF THE GOUY-CHAPMAN THEORy 1 19 Dependence of Surface Potential on Salt Concentration and Surface Charge Density 1 19 Dependence of the Potential on Distancefrom the Membrane Surface.... . . . . . . . . ...... . . . . 122 EXPERIMENTALLY OBSERVED LIMITATIONS OF THE THEORy 123 Discreteness-aI-Charge Eff ects ..... . . . . . . . . . . . . ...... ......... . . .. .. . . . . . . . . . . . . . . ...... . . . . . . . . . . ........ . . . . . '123 Finite Size of Ions. . . . .... . . . . . . . . . . . . . ..... . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . ........ . . . 125 Fixed Charges Displacedfrom the Surface . . . . . . . . . . . . . . ........ 126 Forces Between Char.qed Bilayer Membranes . . . . . . . . ...... . . . . . . . . . . ........ . . . . . 126 ALTERNATIVE THEORIES .. . . . . . . . . . . . . . . . . . . .... . . . . . . . . .... . . ...... . . . . . . . . . . . . . . . . . . . . . ... . . . ...... . . . . . . . .. . . . . ... .. . . 127 Donnan Theory.. . . ....... . . . . . . . . . . . . . . . . .... . . . . . . . . . . . . . . . . . . . . . ........ . . . . . . . . . . . .. . . ..... . . . . 127 Manning Condensation Theory and Geometrical Considerations . . . 127 Modern Statistical Mechanical Theories..... .. . . . . . . . . . . . ..... . . . . . . . . . . . . . . . . ....... . . . . . . . . . . 128 BIOLOGICAL IMPLICATIONS 129 Previous Work.. . . ... . . . . . . . . . ....... . . . . . . . . . . . . . . . . ....... . . . . . . . . . . . .... . . . . . . . . . . . . ....... . . . . . . . . . . . . . .... . . . . . . . . . 129 Future Directions: Surface Potentials and Second Messengers.. .. . .. . . ...... . . . . . . . . . .... . . . . . . 129

Plasma membrane phosphoinositide organization by protein electrostatics

Abstract: Phosphatidylinositol 4,5-bisphosphate (PIP2), which comprises only about 1% of the phospholipids in the cytoplasmic leaflet of the plasma membrane, is the source of three second messengers, activates many ion channels and enzymes, is involved in both endocytosis and exocytosis, anchors proteins to the membrane through several structured domains and has other roles. How can a single lipid in a fluid bilayer regulate so many distinct physiological processes? Spatial organization might be the key to this. Recent studies suggest that membrane proteins concentrate PIP2 and, in response to local increases in intracellular calcium concentration, release it to interact with other biologically important molecules.

PIP2 and Proteins: Interactions, Organization, and Information Flow

Abstract: ▪ Abstract We review the physical properties of phosphatidylinositol 4,5-bisphosphate (PIP2) that determine both its specific interactions with protein domains of known structure and its nonspecific electrostatic sequestration by unstructured domains. Several investigators have postulated the existence of distinct pools of PIP2 within the cell to account for the myriad functions of this lipid. Recent experimental work indicates certain regions of the plasma membrane—membrane ruffles and nascent phagosomes—do indeed concentrate PIP2. We consider two mechanisms that could account for this phenomenon: local synthesis and electrostatic sequestration. We conclude by considering the hypothesis that proteins such as MARCKS bind a significant fraction of the PIP2 in a cell, helping to sequester it in lateral membrane domains, then release this lipid in response to local signals such as an increased concentration of Ca++/calmodulin or activation of protein kinase C.

Electrostatic Potentials at Membrane-Solution Interfaces

Abstract: Publisher Summary This chapter discusses electrostatic potentials at membrane solution interfaces. Lipids in the membranes of all cells and subcellular organelles are arranged in the form of a bilayer with the hydrocarbon tails sequestered away from the water and the polar head groups exposed to the aqueous environment. About 10%–20% of the lipids in the membranes of many cells and organelles bear a net negative charge, whereas positively charged lipids are extremely rare. The concentration of monovalent cations at the surface of the bilayer will be an order of magnitude higher than the concentration of these ions in the bulk aqueous phase. The surface potential produced by charged lipids is dependent on the salt concentration in the bulk aqueous phase and a seminal paper. The absence of proteins, polysaccharides, and other macromolecules present in biological membranes can be considered an advantage to test how well the theory of the diffuse double layer describes the electrostatic potential produced by charges on lipids. The chapter describes hydrophobic adsorption of charged molecules to bilayer membranes, the electrostatic potential produced by molecular dipoles at membrane-solution interfaces, and the electrostatic boundary potential produced by charges located in the interior of the membrane, a few angstroms from the interface. Few examples of the possible biological significance of these electrostatic surface potentials are also described.

Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans

Abstract: Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression Here we investigate the requirements for structure and delivery of the interfering RNA To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference The effects of this interference were evident in both the injected animals and their progeny Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process

Phosphoinositides in cell regulation and membrane dynamics

Abstract: Inositol phospholipids have long been known to have an important regulatory role in cell physiology. The repertoire of cellular processes known to be directly or indirectly controlled by this class of lipids has now dramatically expanded. Through interactions mediated by their headgroups, which can be reversibly phosphorylated to generate seven species, phosphoinositides play a fundamental part in controlling membrane-cytosol interfaces. These lipids mediate acute responses, but also act as constitutive signals that help define organelle identity. Their functions, besides classical signal transduction at the cell surface, include regulation of membrane traffic, the cytoskeleton, nuclear events and the permeability and transport functions of membranes.

TRP channels as cellular sensors

Abstract: TRP channels are the vanguard of our sensory systems, responding to temperature, touch, pain, osmolarity, pheromones, taste and other stimuli. But their role is much broader than classical sensory transduction. They are an ancient sensory apparatus for the cell, not just the multicellular organism, and they have been adapted to respond to all manner of stimuli, from both within and outside the cell.

Automated Solution of Differential Equations by the Finite Element Method: The FEniCS Book

Abstract: This book is a tutorial written by researchers and developers behind the FEniCS Project and explores an advanced, expressive approach to the development of mathematical software. The presentation spans mathematical background, software design and the use of FEniCS in applications. Theoretical aspects are complemented with computer code which is available as free/open source software. The book begins with a special introductory tutorial for beginners. Followingare chapters in Part I addressing fundamental aspects of the approach to automating the creation of finite element solvers. Chapters in Part II address the design and implementation of the FEnicS software. Chapters in Part III present the application of FEniCS to a wide range of applications, including fluid flow, solid mechanics, electromagnetics and geophysics.