Alex Levine - Profile on Academia.edu (original) (raw)

Papers by Alex Levine

We report on the surface rheology of cross-linked F-actin networks associated with a lipid monola... more We report on the surface rheology of cross-linked F-actin networks associated with a lipid monolayer at the air-water interface of a Langmuir monolayer. The rheological measurements are made using a Couette cell. These data demonstrate that the network has a finite elastic modulus that grows as a function of the cross-linking concentration. We also note that under steady-state flow the system behaves as a power law fluid in which the effective viscosity decreases with imposed shear.

Proceedings of the National Academy of Sciences of the United States of America, Mar 27, 2017

The thermal fluctuations of membranes and nanoscale shells affect their mechanical characteristic... more The thermal fluctuations of membranes and nanoscale shells affect their mechanical characteristics. Whereas these fluctuations are well understood for flat membranes, curved shells show anomalous behavior due to the geometric coupling between in-plane elasticity and out-of-plane bending. Using conventional shallow shell theory in combination with equilibrium statistical physics we theoretically demonstrate that thermalized shells containing regions of negative Gaussian curvature naturally develop anomalously large fluctuations. Moreover, the existence of special curves, "singular lines," leads to a breakdown of linear membrane theory. As a result, these geometric curves effectively partition the cell into regions whose fluctuations are only weakly coupled. We validate these predictions using high-resolution microscopy of human red blood cells (RBCs) as a case study. Our observations show geometry-dependent localization of thermal fluctuations consistent with our theoretica...

Fibroblast growth factor 2 dimer with superagonist in vitro activity improves granulation tissue formation during wound healing

Biomaterials, Jan 15, 2015

Site-specific chemical dimerization of fibroblast growth factor 2 (FGF2) with the optimal linker ... more Site-specific chemical dimerization of fibroblast growth factor 2 (FGF2) with the optimal linker length resulted in a FGF2 homodimer with improved granulation tissue formation and blood vessel formation at exceptionally low concentrations. Homodimers of FGF2 were synthesized through site-specific linkages to both ends of different molecular weight poly(ethylene glycols) (PEGs). The optimal linker length was determined by screening dimer-induced metabolic activity of human dermal fibroblasts and found to be that closest to the inter-cysteine distance, 70 Å, corresponding to 2 kDa PEG. A straightforward analysis of the kinetics of second ligand binding as a function of tether length showed that, as the polymerization index (the number of monomer repeat units in the polymer, N) of the tether decreases, the mean time for second ligand capture decreases as ∼N(3/2), leading to an enhancement of the number of doubly bound ligands in steady-state for a given (tethered) ligand concentration....

Oxidative Stress and DNA Modifications in Plants

Filamin cross-linkers as rheology regulators in biopolymer networks

We report on the nonlinear mechanical properties of a statistically homogeneous, isotropic semifl... more We report on the nonlinear mechanical properties of a statistically homogeneous, isotropic semiflexible network cross-linked by polymers containing numerous small unfolding domains. This model captures the main mechanical features of F-actin networks cross-linked by filamin proteins, which contain twenty-four such Ig-domains that may unfold under applied strain. We show that under sufficiently high strain the network spontaneously organizes itself so that an appreciable fraction of the filamin cross-linkers are at the threshold of domain unfolding. We discuss via a simple model the cause of this network organization. We also discuss how observation of this critical state validates a mechanism proposed by Crocker et al. to explain the weak power law dependence of the measured strain modulus as observed in intracellular microrheology experiments.

H2O2-Mediated Oxidative Cross-Linking of Cell Wall Structural Proteins

Current Plant Science and Biotechnology in Agriculture, 1994

ABSTRACT

The effect of geometry on membrane undulations: Scattering of undulatory waves and applications to the membrane fluctuations of red blood cells

ABSTRACT We report on calculations regarding the effects of geometry on the dynamics of small und... more ABSTRACT We report on calculations regarding the effects of geometry on the dynamics of small undulations of an elastic membrane. From the work of Vaziri and Mahadevan (PNAS 105 7913, 2008) it is well understood that the Green's function (i.e. point indentation response) of the membrane changes character when the Gaussian curvature of the undeformed membrane changes sign. For positive Gaussian curvature, the effective linearized equation for the deformation is elliptic, but it is hyperbolic in the case of negative Gaussian curvature. We examine the dynamical generalization of this analysis by calculating the reflection and refraction of membrane undulatory waves when passing from a region of one geometry to another. We also examine the effect of lines of zero Gaussian curvature (separating regions of positive and negative Gaussian curvature) on the normal mode spectrum of a model discocyte and apply this analysis to understanding the membrane undulations of red blood cells, as measured by Park et al. (PNAS 107 6731, 2010).

Conceptual Change: Analogies Great and Small and the Quest for Coherence

International Handbook of Research in History, Philosophy and Science Teaching, 2013

Partition epistemology and arguments from analogy

Synthese, 2009

... Alex Levine ... Thomas Kuhn, in his 1962 Structure of Scientific Revolutions, initiated a sig... more ... Alex Levine ... Thomas Kuhn, in his 1962 Structure of Scientific Revolutions, initiated a signif-icant change in how philosophers of science think of scientific change, and of the scientific communities, scientific theories, and scientific explanations that experience such change. ...

Science, 2006

We studied the kinetics of sublimating crystals with single-particle resolution by experiments wi... more We studied the kinetics of sublimating crystals with single-particle resolution by experiments with colloidal spheres and by computer simulations. A short-range attraction between spheres led to crystallites one to three layers thick. The spheres were tracked with optical microscopy while the attraction was reduced and the crystals sublimated. Large crystallites sublimated by escape of particles from the perimeter. The rate of shrinkage was greatly enhanced, however, when the size decreased to less than 20 to 50 particles, depending on the location in the phase diagram. At this size, the crystallites transformed into a dense amorphous structure, which rapidly vaporized. The enhancement of kinetics by metastable or unstable phases may play a major role in the melting, freezing, and annealing of crystals.

Protein Expression and Purification, 1999

Cysteine proteases are implicated in many regulatory and degradative processes in animal and plan... more Cysteine proteases are implicated in many regulatory and degradative processes in animal and plant cells. Many of the proteases are strongly inhibited by an irreversible inhibitor, trans-(epoxysuccinyl)-Lleucylamino-4-guanidinobutane (E-64) from Aspergillus japonicus. Here we report a method for purification of cysteine proteases by affinity chromatography on E-64. Attachment of the inhibitor to thiopropyl Sepharose through its epoxy group resulted in the loss of its irreversible activity but did not affect the specificity of interaction or its capability to bind cysteine proteases. Papain that served as a model cysteine protease was fully active after elution. We also provide evidence for purification of active proteases from a mixture of extracellular fluid of Botrytis cinerea-and Trichoderma harzianum-inoculated bean plants. Since the proteases are eluted with urea after the column is washed with 1 M NaCl, this procedure may provide highly efficient purification.

Physical Review Letters, 2012

Because of its ability to study specifically labeled structures, fluorescence microscopy is the m... more Because of its ability to study specifically labeled structures, fluorescence microscopy is the most widely used technique for investigating live cell dynamics and function. Fluorescence correlation spectroscopy is an established method for studying molecular transport and diffusion coefficients at a fixed spatial scale. We propose a new approach, dispersion-relation fluorescence spectroscopy (DFS), to study the transport dynamics over a broad range of spatial and temporal scales. The molecules of interest are labeled with a fluorophore whose motion gives rise to spontaneous fluorescence intensity fluctuations that are analyzed to quantify the governing mass transport dynamics. These data are characterized by the effective dispersion relation. We report on experiments demonstrating that DFS can distinguish diffusive from advection motion in a model system, where we obtain quantitatively accurate values of both diffusivities and advection velocities. Because of its spatially resolved information, DFS can distinguish between directed and diffusive transport in living cells. Our data indicate that the fluorescently labeled actin cytoskeleton exhibits active transport motion along a direction parallel to the fibers and diffusive in the perpendicular direction.

Physical Review Letters, 1998

A coarse-grained stochastic hydrodynamical description of velocity and concentration fluctuations... more A coarse-grained stochastic hydrodynamical description of velocity and concentration fluctuations in steadily sedimenting suspensions is constructed, and analyzed using self-consistent and renormalization group methods. We find that there exists a dynamical, non-equilibrium phase transition from a "unscreened" phase in which we recover the Calflisch-Luke (R.E. Calflisch and J.H.C. Luke, Phys. Fluids 28, 759 (1985)) divergence of the velocity variance to a "screened" phase where the velocity fluctuations have a finite correlation length growing as φ -1/3 where φ is the particle volume fraction, in agreement with Segrè et al. (Phys. Rev. Lett. 79, 2574) and the velocity variance is independent of system size. Detailed predictions are made for the correlation function in both phases and at the transition.

Physical Review E, 2006

We study a minimal extension of the worm-like chain to describe polypeptides having alphahelical ... more We study a minimal extension of the worm-like chain to describe polypeptides having alphahelical secondary structure. In this model presence/absence of secondary structure enters as a scalar variable that controls the local chain bending modulus. Using this model we compute the extensional compliance of an alpha-helix under tensile stress, the bending compliance of the molecule under externally imposed torques, and the nonlinear interaction of such torques and forces on the molecule. We find that, due to coupling of the "internal" secondary structure variables to the conformational degrees of freedom of the polymer, the molecule has a highly nonlinear response to applied stress and force couples. In particular we demonstrate a sharp lengthening transition under applied force and a buckling transition under applied torque. Finally, we speculate that the inherent bistability of the molecule may underlie protein conformational change in vivo.

Physical Review E, 2009

Large scale, discrete element simulations are performed to study the dynamics of a rotating drum ... more Large scale, discrete element simulations are performed to study the dynamics of a rotating drum partially filled with cohesive granular particles. The continuous avalanche regime is explored using a simple model for interparticle cohesion in order to simulate the effects of granular media in the presence of a wetting fluid. The shape of the free surface for cohesionless particles ranges from flat to a concave S shape depending on the rotation rate and frictional properties between the grains and the drum side walls. The presence of interparticle cohesion reduces the concavity of the free surface and pushes the free surface towards a flat or even slightly convex shape. From contour plots of the velocity, we show how the position of the vortex core ͑the stationary spot in the laboratory frame͒ depends on the rotation speed and interparticle cohesion strength and how this relationship can be understood from considerations of the incompressibility condition on the mass flow.

Concepts: Where Fodor Went Wrong

Philosophical Psychology, 1999

In keeping with other recent efforts, Fodor&#x27;s CONCEPTS focuses on the metaphysics of... more In keeping with other recent efforts, Fodor&#x27;s CONCEPTS focuses on the metaphysics of conceptual content, bracketing such epistemological questions as,&quot; How can we know the contents of our concepts?&quot; Fodor&#x27;s metaphysical account of concepts, called&quot; informational atomism,&quot; stipulates that the contents of a subject&#x27;s concepts are fixed by the nomological lockings between the subject and the world. After sketching Fodor&#x27;s&quot; what else?&quot; argument in support of this view, we offer a number of related criticisms. All point to the same ...

Journal of Biological Chemistry, 2001

Programmed cell death (PCD) in many systems is controlled by relative amounts of the apoptosis-re... more Programmed cell death (PCD) in many systems is controlled by relative amounts of the apoptosis-regulating proteins Bax and Bcl-2 through homo-or heterodimerization. Here we show that Bax-induced PCD of yeast was suppressed by transformation with a vesicle-associated membrane protein from Arabidopsis (AtVAMP), which was isolated by screening a cDNA expression library against sugar-induced cell death in yeast. At-VAMP expression blocked Bax-induced PCD downstream of oxidative burst. AtVAMP also prevented H 2 O 2induced apoptosis in yeast and in Arabidopsis cells. Reduced oxidation of lipids and plasma membrane proteins was detected in the AtVAMP-transformed yeast, suggesting improved membrane repair. Inhibition of intracellular vesicle trafficking by brefeldin A induced apoptosis from a sublethal concentration of H 2 O 2 . No protection occurred by overexpression of the yeast homolog SCN2. However, efficient suppression of yeast PCD occurred by expression of a chimeric gene, composed of the conserved domains from yeast, fused to the variable N-terminal domain from Arabidopsis, resulting in exchange of the proline-rich N-terminal domain of SCN2 with a proline-poor Arabidopsis sequence. Our results suggest that intracellular vesicle traffic can regulate execution of apoptosis by affecting the rate of membrane recycling and that the proline-rich N-terminal domain of VAMP inhibited this process.

Current Biology, 2002

Jerusalem isms, suggesting allelopathic interactions. Inhibition of photosynthesis in P. gatunens... more Jerusalem isms, suggesting allelopathic interactions. Inhibition of photosynthesis in P. gatunense by Microcystis sp. [7] 2 Oceanographic & Limnological Research P.O. Box 447 supported this notion. This was further confirmed in long-term growth experiments that indicated reciprocal 14950 Migdal Israel inhibition of P. gatunense growth in the presence of Microcystis sp. and vice versa. When the initial P. gatunense inoculum was 200 cells/ml, its growth was completely inhibited by the presence of Microcystis sp. MG Summary (10 6 cells/ml), even when amply supplemented with nutrients. In similar experiments in which the initial P. gatu-The reasons for annual variability in the composition nense inoculum was raised to 560 cells/ml, growth was of phytoplankton assemblages are poorly understood 60% inhibited. In contrast, when the initial density of but may include competition for resources and allelo-P. gatunense was 2300 cells/ml, growth was scarcely pathic interactions [1-4]. We show that domination by affected by Microcystis sp. (not shown). Conversely, the patch-forming dinoflagellate, Peridinium gatugrowth of Microcystis sp. was hardly affected by the nense, or, alternatively, a bloom of a toxic cyanobactpresence of P. gatunense as long as the initial inoculum erium, Microcystis sp., in the Sea of Galilee [5] may of the latter did not exceed 1000 cells/ml, but growth be accounted for by mutual density-dependent allelowas severely depressed when higher cell densities of pathic interactions. Over the last 11 years, the abun-P. gatunense were applied (Figure ), even in the presdance of these species in the lake displayed strong ence of an adequate nutrient supply. These data sugnegative correlation. Laboratory experiments showed gested that allelopathic interactions between these orreciprocal, density-dependent, but nutrient-indepenganisms were density dependent and affected their dent, inhibition of growth. Application of spent P. gatulong-term growth. nense medium induced sedimentation and, subsequently, massive lysis of Microcystis cells within 24 hr, and sedimentation and lysis were concomitant with Induction of Oxidative Stress in Peridinium a large rise in the level of McyB, which is involved in by Microcystis toxin biosynthesis by Microcystis [6]. P. gatunense To examine more immediate responses of P. gatunense responded to the presence of Microcystis by a speto Microcystis sp., we measured the accumulation of cies-specific pathway that involved a biphasic oxidareactive oxygen species (ROS), which reflect stress retive burst and activation of certain protein kinases. sponses in P. gatunense [8] and other aquatic photosyn-Blocking this recognition by MAP-kinase inhibitors thetic organisms [9, 10]. The fraction of P. gatunense abolished the biphasic oxidative burst and affected cells that contained ROS increased significantly within the fate (death or cell division) of the P. gatunense 0.5 hr after the addition of Microcystis MG (Figures 2A cells. We propose that patchy growth habits may con- and). The level of ROS-positive cells reached a first fer enhanced defense capabilities, providing ecologimaximum in about 1 hr, followed by a secondary oxidacal advantages that compensate for the aggravated tive burst that reached a maximum within 24 hr and then limitation of resources in the patch. Cross-talk via aldeclined to the initial level (Figure ). Application of lelochemicals may explain the phytoplankton assemmicrocystin-LR, a hepatotoxin that inhibits protein blage in the Sea of Galilee. phosphatases types 1 and 2A [11, 12], the main toxin produced by Microcystis MG, also resulted in a typical Results and Discussion biphasic pattern, but the second maximum was reached considerably faster (Figure ). By contrast, the addition Annual blooms of P. gatunense have dominated the of Microcystis MB, which does not produce detectable phytoplankton assemblage in the Sea of Galilee for many amounts of microcystins, scarcely affected the initial years. Deterioration of this stability during the last de-ROS level in P. gatunense and did not induce a secondcade (Figure ) was indicated by delays, or even abary oxidative burst. The amplitude and the exact timing sence, of P. gatunense patches. Examination of the of the biphasic responses observed were affected by abundances of P. gatunense and Microcystis sp. in the various growth conditions. For example, the ratio be-Sea of Galilee over the last 11 years (Figure ) provided tween the primary and the secondary ROS-positive the first indication that these disturbances were correpeaks increased with the age of the culture (compare lated with the appearance of Microcystis sp. Statistical the data in Figure with Figure ). Further, while the Microcystis treatment of older cultures such as those used in Figure resulted in approximately 30% sytox-