Popular science articles

A Mobile Precursor Determines Amyloid-β Peptide Fibril Formation at Interfaces

Lei Shen , Takuji Adachi , David Vanden Bout , and X.-Y. Zhu * Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, United States J. Am. Chem. Soc., Article ASAP DOI: 10.1021/ja305398f Publication Date (Web): August 6, 2012 Copyright © 2012 American Chemical Society zhu@cm.utexas.edu

The aggregation of peptides into amyloid fibrils plays a crucial role in various neurodegenerative diseases. While it has been generally recognized that fibril formation in vivo may be greatly assisted or accelerated by molecular surfaces, such as cell membranes, little is known about the mechanism of surface-mediated fibrillation. Here we study the role of adsorbed Alzheimer’s amyloid-β peptide (Aβ42) on surface-mediated fibrillation using polymer coatings of varying hydrophobicity as well a supported lipid bilayer membrane. Using single molecule fluorescent tracking and atomic force microscopy imaging, we show that weakly adsorbed peptides with two-dimensional diffusivity are critical precursors to fibril growth on surfaces. This growth mechanism is inhibited on the highly hydrophilic surface where the surface coverage of adsorbed peptides is negligible or on the highly hydrophobic surface where the diffusion constant of the majority of adsorbed peptides is too low. Physical properties that favor weakly adsorbed peptides with sufficient translational mobility can locally concentrate peptide molecules on the surface and promote inter-peptide interaction via two-dimensional confinement, leading to fibrillation at Aβ peptide concentration many orders of magnitude below the critical concentration for fibrillation in the bulk solution.

A Mechano-Electronic DNA Switch

Jason M. Thomas †‡, Hua-Zhong Yu *‡, and Dipankar Sen *†‡

^‡Department of Chemistry and ^†Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6

J. Am. Chem. Soc., Article ASAP

DOI: 10.1021/ja303530y

Publication Date (Web): July 26, 2012

sen@sfu.ca; hzyu@sfu.ca

We report a new kind of DNA nanomachine that, fueled by Hg²⁺ binding and sequestration, couples mechanical motion to the multiply reversible switching of through-DNA charge transport. This mechano-electronic DNA switch consists of a three-way helical junction, one arm of which is a T-T mismatch containing Hg²⁺-binding domain. We demonstrate, using chemical footprinting and by monitoring charge-flow-dependent guanine oxidation, that the formation of T-Hg²⁺-T base pairs in the Hg²⁺-binding domain sharply increases electron–hole transport between the other two Watson–Crick-paired stems, across the three-way junction. FRET measurements are then used to demonstrate that Hg²⁺ binding/dissociation, and the concomitant increase/decrease of hole transport efficiency, are strongly linked to specific mechanical movements of the two conductive helical stems. The increase in hole transport efficiency upon Hg²⁺ binding is tightly coupled to the movement of the conductive stems from a bent arrangement toward a more linear one, in which coaxial stacking is facilitated. This switch offers a paradigm wherein the performance of purely mechanical work by a nanodevice can be conveniently monitored by electronic measurement.

False-colored scanning electron microscopy image of innate immune cells and the parasite Trypanosoma brucei

Aqueous Multiphase Systems of Polymers and Surfactants Provide Self-Assembling Step-Gradients in Density

Charles R. Mace†, Ozge Akbulut†, Ashok A. Kumar‡, Nathan D. Shapiro†, Ratmir Derda†, Matthew R. Patton†, and George M. Whitesides*†§

J. Am. Chem. Soc., 2012, 134 (22), pp 9094–9097

DOI: 10.1021/ja303183z

Publication Date (Web): May 17, 2012

This Communication demonstrates the generation of over 300 phase-separated systems—ranging from two to six phases—from mixtures of aqueous solutions of polymers and surfactants. These aqueous multiphase systems (MuPSs) form self-assembling, thermodynamically stable step-gradients in density using a common solvent, water. The steps in density between phases of a MuPS can be very small (Δρ ≈ 0.001 g/cm³), do not change over time, and can be tuned by the addition of co-solutes. We use two sets of similar objects, glass beads and pellets of different formulations of Nylon, to demonstrate the ability of MuPSs to separate mixtures of objects by differences in density. The stable interfaces between phases facilitate the convenient collection of species after separation. These results suggest that the stable, sharp step-gradients in density provided by MuPSs can enable new classes of fractionations and separations based on density.

Analog modeling of Worm-Like Chain molecules using macroscopic beads-on-a-string†

Simon Tricard *a, Efraim Feinstein b, Robert F. Shepherd a, Meital Reches a, Phillip W. Snyder a, Dileni C. Bandarage a, Mara Prentiss b and George M. Whitesides *ac
Current computational simulations can not accurately quantify the very large number of interactions and conformations required to describe molecular phenomena (for example, polymer dynamics, solvation, crystal nucleation and growth, molecular recognition, etc.). Descriptions of the kinetics of dynamic phenomena are mostly unapproachable without drastic simplifications. Assumptions and approximations – some major – are required to make aspects of static and equilibrium problems tractable for theoretical modeling or simulation. Although we applaud the value of digital, computational models, we also believe that analog, physical methods1–4 have a role to play in understanding molecular (and supramolecular) phenomena, and we are exploring such models as a complement to theory and in silico simulation.

Behaviour of polydiacetylene vesicles under different conditions of temperature, pH and chemical components of milk

Cristiane Patrícia de Oliveira^a^,,
Nilda de Fátima Ferreira Soares^b^,^,,
Edimar Aparecida Filomeno Fontes^b^,,
Taíla Veloso de Oliveira^b^,,
Antônio Manoel Maradini Filho^b^,

Received 21 February 2012. Revised 17 May 2012. Accepted 20 May 2012. Available online 28 May 2012.

Abstract

Blue polydiacetylene vesicles were studied with regard to their behaviour under variations in storage temperature, heating, potentiometric titration and in the presence of chemical components of milk, to evaluate their application as a sensor in the food industry. Vesicles were prepared using 10,12-pentacosadienoic acid (PCDA)/1,2- dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC). Their changes were monitored using UV-Vis absorption. Temperatures not exceeding 25 °C did not cause colour change in PCDA/DMPC vesicles for a period of up to 60 days of storage. Heating for 10 minutes at 60 and 90 °C, exposure to pH higher than 9.0 and the simulant solutions of the whey proteins, β-lactoglobulin and α-lactalbumin, promoted colour change from blue to red for the vesicles studied. The effects of routine factors on the characteristics and stability of polydiacetylene vesicles is important in defining the parameters related to their application as a sensor for the food industry.