Biomedical subjects

Peter Lenz

Publications and source records attributed to Peter Lenz.

11 recordsLinked to original sources

PubMed2006

Collective effects in ciliar arrays.

Collective effects in one-dimensional ciliar arrays are studied analytically and numerically. A new phase oscillator description for ciliar motion is introduced which depends only on a single parameter. It allows the systematic study of hydrodynamic interactions between cilia exhibiting arbitrary beating patterns. It is shown that if the hydrodynamic interactions do not alter the beating pattern of the cilia no synchronization of ciliar motion occurs. This is in particular the case in arrays with low ciliar densities. But hydrodynamic interactions can lead to formation of a collective (metachronal) wave which is stable for periodic boundary conditions. In finite arrays free boundaries destroy this collective motion. The dispersion relation for metachronal waves is found to be non-universal, i.e., to depend crucially on the microscopic details of the ciliar beating pattern.

Animals↗

PubMed2006

An entropic mechanism to generate highly cooperative and specific binding from protein phosphorylations.

Cooperative interactions are essential to the operation of many biochemical networks. Such networks then respond ultrasensitively in a nonlinear manner to linear changes in network input, and network output, for example, levels of a phosphorylated protein or of gene expression, becomes a sigmoidal function of concentrations of input molecules. We present a novel, entropic ultrasensitivity mechanism that generates highly cooperative and specific binding between two proteins. We consider a disordered protein with multiple phosphorylation sites that binds to a single binding site on an interacting protein. We assume that each phosphorylation locally orders the protein. Such local order affects protein conformational entropy nonlinearly and generates binding that is a highly cooperative function of the number of protein phosphorylations (with Hill coefficients well above 10). Substantial binding may only occur once the disordered protein is phosphorylated a critical number of times or more. Cooperativity is determined by the size of the disordered region of the protein, the binding affinity, and unusually the concentration of the interacting protein. Given the widespread occurrence of disordered, multiply phosphorylated proteins, its highly ultrasensitive character, and the ease of its control, entropic, phosphorylation-driven cooperativity may be extensively exploited intracellularly.

Binding Sites↗

PubMed2006

Diffusive dynamics of vesicles tethered to a fluid supported bilayer by single-particle tracking.

We recently introduced a method to tether intact phospholipid vesicles onto a fluid supported lipid bilayer using DNA hybridization (Yoshina-Ishii, C.; Miller, G. P.; Kraft, M. L; Kool, E. T.; Boxer, S. G. J. Am. Chem. Soc. 2005, 127, 1356-1357). Once tethered, the vesicles can diffuse in two dimensions parallel to the supported membrane surface. The average diffusion coefficient, D, is typically 0.2 microm(2)/s; this is 3-5 times smaller than for individual lipid or DNA-lipid conjugate diffusion in supported bilayers. In this article, we investigate the origin of this difference in the diffusive dynamics of tethered vesicles by single-particle tracking under collision-free conditions. D is insensitive to tethered vesicle size from 30 to 200 nm, as well as a 3-fold change in the viscosity of the bulk medium. The addition of macromolecules such as poly(ethylene glycol) reversibly stops the motion of tethered vesicles without causing the exchange of lipids between the tethered vesicle and supported bilayer. This is explained as a depletion effect at the interface between tethered vesicles and the supported bilayer. Ca ions lead to transient vesicle-vesicle interactions when tethered vesicles contain negatively charged lipids, and vesicle diffusion is greatly reduced upon Ca ion addition when negatively charged lipids are present both in the supported bilayer and tethered vesicles. Both effects are interesting in their own right, and they also suggest that tethered vesicle-supported bilayer interactions are possible; this may be the origin of the reduction in D for tethered vesicles. In addition, the effects of surface defects that reversibly trap diffusing vesicles are modeled by Monte Carlo simulations. This shows that a significant reduction in D can be observed while maintaining normal diffusion behavior on the time scale of our experiments.

4-Chloro-7-nitrobenzofurazan↗

PubMed2004

Vesicle adsorption and lipid bilayer formation on glass studied by atomic force microscopy.

The adsorption of phosphatidylcholine (PC) vesicles (30, 50, and 100 nm nominal diameters) and of dye-labeled PC vesicles (labeled with 6% Texas Red fluorophore (TR) and encapsulated carboxy fluorescein (CF)) to glass surfaces was studied by contact mode atomic force microscopy in aqueous buffer. These studies were performed in part to unravel details of the previously observed isolated rupture of dye-labeled PC vesicles on glass (Johnson, J. M.; Ha, T.; Chu, S.; Boxer, S. G. Biophys. J. 2002, 83, 3371-3379), specifically to differentiate partial rupture, that is, pore formation and leakage of entrapped dye, from full rupture to form bilayer disks. In addition, the adhesion potential of PC vesicles on glass was calculated based upon the adhesion-driven flattening of adsorbed vesicles and a newly developed theoretical model. The vesicles were found to flatten considerably upon adsorption to glass (width-to-height ratio of approximately 5), which leads to an estimate for the adhesion potential and for the critical rupture radius of 1.5 x 10(-4) J/m2 and 250 nm, respectively. Independent of vesicle size and loading with dye molecules, the adsorption of intact vesicles was observed at all concentrations below a threshold concentration, above which the formation of smooth lipid bilayers occurred. In conjunction with previous work (Johnson, J. M.; Ha, T.; Chu, S.; Boxer, S. G. Biophys. J. 2002, 83, 3371-3379), these data show that 6% TR 20 mM CF vesicles adsorb to the surface intact but undergo partial rupture in which they exchange content with the external buffer.

Adsorption↗

PubMed2004

Patterned supported lipid bilayers and monolayers on poly(dimethylsiloxane).

A simple and practical method for patterning supported lipid bilayers on poly(dimethylsiloxane) is presented. By using electron microscopy grids to laterally control the extent of plasma oxidation, the substrate is partitioned into regions of different hydrophilicities. Addition of vesicles then results in the spontaneous formation of lipid bilayers and monolayers side-by-side on the surface, separated by regions that contain no lipid and/or a region with adhering vesicles. By using millimeter-sized plastic masks we are able to control the formation of these lipid structures on macroscopic patches by simply varying the plasma-cleaning time. For the first time, we are able to influence, in a controlled fashion, the chemical composition of a substrate in such a way that it supports fluid lipid monolayers, rejects lipid adhesion, adsorbs intact lipid vesicles, or supports fluid bilayers.

Dimethylpolysiloxanes↗

PubMed2004

Folding probabilities: a novel approach to folding transitions and the two-dimensional Ising-model.

The theoretical concept of folding probability, p(fold), has proven to be a useful means to characterize the kinetics of protein folding. Here, we illustrate the practical importance of p(fold) and demonstrate how it can be determined theoretically. We derive a general analytical expression for p(fold) and show how it can be estimated from simulations for systems where the transition rates between the relevant microstates are not known. By analyzing the Ising model we are able to determine the scaling behavior of the numerical error in the p(fold) estimate as function of the number of analyzed Monte Carlo runs. We apply our method to a simple, newly developed protein folding model for the formation of alpha helices. It is demonstrated that our technique highly parallelizes the calculation of p(fold) and that it is orders of magnitude more efficient than conventional approaches.

Algorithms↗

PubMed2004

Prognostic role of CD8+ tumor-infiltrating lymphocytes in stage III colorectal cancer with and without microsatellite instability.

Previous studies have identified high numbers of intraepithelial T lymphocytes to be associated with good prognosis in various types of cancer. Few studies addressing this issue have been published for colorectal cancer. In a simulated prospective approach ("phase II prognostic factor study"), all nonmetachronous International Union Against Cancer (UICC) stage III colorectal cancers that were accessioned in the years 1994 to 1999 were included in the study (152 cases). Follow-up information as to vital status and occurrence of metachronous metastases could be obtained for all patients in the years 2001 and 2002. CD8+ intratumoral lymphocytes were quantified after immunostaining and referred to tumor cell area (CD8+ densities). Microsatellite status was determined by using the Bethesda panel of microsatellite markers. CD8+ densities ranged from 0 per square millimeter to 1436 per square millimeter of tumor area in a nonnormal distribution that was skewed toward low values. Univariate survival analyses revealed the 66th percentile as a stringent cutoff (CD8+high versus CD8+low), with CD8+high cases taking a significantly better clinical course. This prognostic impact appeared even more pronounced in the subset of patients with colon carcinomas who were receiving 5-fluouracil/leucovorin as adjuvant treatment (79 patients). Seventeen patients had carcinomas with high microsatellite instability (MSI-H). MSI-H-CD8+high cases (n = 11) showed an excellent prognosis, with tumor-free survival for 9 of the 11 patients. The prognostic effect of CD8+high was retained in Cox regression analyses when including UICC substages (IIIA to IIIC). Our results identify CD8+ tumor-infiltrating lymphocytes as a promising candidate for further evaluation in the ongoing search for prognostic and predictive factors of colorectal cancer, particularly if combined with microsatellite status.

Adenocarcinoma, Mucinous↗

PubMed2004

Determination of the acoustic pressure at and the reflection coefficient of a target through measurements of the absorbed power and the emitter voltage.

A harmonic acoustic wave, fed back by a reflecting target, modifies the electric impedance of the emitter. This effect is studied using a tightly focused beam and various flat targets with known reflection coefficients, which are placed at pressure maxima or minima of the standing wave in the focal zone. It is possible to establish relationships that allow one to determine, for flat targets with unknown acoustic properties, the acoustic impedance and reflection coefficient of the target as well as the acoustic pressure present at the target, only from measurements of the absorbed power and the emitter voltage.

Acoustics↗

PubMed2003

Membranes with rotating motors.

We study collections of rotatory motors confined to two-dimensional manifolds. These systems show a nontrivial collective behavior since the rotational motion leads to a repulsive hydrodynamic interaction between motors. While for high rotation speed motors might exhibit crystalline order, they form at low speed a disordered phase where diffusion is enhanced by velocity fluctuations. These effects should be experimentally observable for motors driven by external fields and for dipolar biological motors embedded into lipid membranes in a viscoelastic solvent.

Adenosine Triphosphatases↗

PubMed2003

Hexatic undulations in curved geometries.

We discuss the influence of two-dimensional hexatic order on capillary waves and undulation modes in spherical and cylindrical geometries. In planar geometries, extended bond-orientational order has only a minor effect on the fluctuations of liquid surfaces or lipid bilayers. However, in curved geometries, the long-wavelength spectrum of these ripples is altered. We calculate this frequency shift and discuss applications to spherical vesicles, liquid metal droplets, bubbles and cylindrical jets coated with surface-active molecules, and to multielectron bubbles in liquid helium at low temperatures. Hexatic order also leads to a shift in the threshold for the fission instability of charged droplets and bubbles, and for the Plateau-Rayleigh instability of liquid jets.

Journal Article↗

PubMed2003

Long-lasting stable cavitation.

Stable cavitation is produced on the surface of a special target, i.e., an abrasive foil with a grain size of about 15 microm, insonified by a 473 kHz focused beam. Cavitation bubbles are first created by a pressure of about 2 MPa. Progressive reduction of the pressure to about 100 kPa leads to a state of stable cavitation characterized by strong stable emission of the half-order subharmonic. This state can be maintained for five hours if the defining parameters (position and pressure) are optimized and constant to within a few percent. There is strong evidence for the presence of "latent" cavitation bubbles, which can persist for a few minutes without being excited.

Journal Article↗