Biological and Soft Matter Seminar at TAU
Seminars of 2010-2011

December 1st 2010: Roy Beck (TAU)
Unconventional Salt-Switch from Soft to Stiff in Single Neurofilament Biopolymers

Neurofilaments (NFs) – the major cytoskeletal constituent of myelinated axons in vertebrates – consist of three molecular-weight subunit proteins NF-L (low), NF-M (medium), and NF-H (high), assembled to form mature filaments with protruding unstructured C-terminus sidearms. Liquid crystal gel networks of sidearm-mediated NF assemblies play a key role in the mechanical stability of neuronal processes. Disruptions of the NF-network, due to NF over-accumulation or incorrect sidearm interactions, is a hallmark of motor neuron diseases including amyotrophic lateral sclerosis. In this talk I will present our recent tapping mode atomic force microscopy study on single NFs. We traced, in sub-pixel resolution, photo-immobilized NFs and measured their persistence length at various monovalent salt conditions and at various subunit protein ratios thereby modifying sidearm length and chain density charge distribution. I will show that specific polyampholyte sequences of the sidearms can form salt switchable intra-filament attractions that compete with the net electrostatic and steric repulsion, and can reduce the total persistence length by half. The results are in agreement with present x-ray and microscopy data, yet present a theoretical challenge for polyampholyte inter-chain interactions.

December 8th 2010: Robert Blumenthal (NIH)
Nanochemistry in membranes: Applications to chemotherapy and vaccines


December 15th 2010: David Sprinzak (TAU)
To send or receive but not both: An inter-cellular signaling switch for multi-cellular pattern formation

How complex patterns of cells are generated during embryonic development has been a central question in science for centuries. In the past few decades many of the molecular components involved in these processes (signaling molecules, genes, and proteins) and their interactions have been identified allowing us to draw detailed genetic networks underlying many of these processes. However, it is often unclear how these genetic networks give rise to the observed patterns and what are the ‘design principles’ underlying these networks. In this talk, I will describe the experimental and theoretical analysis of a class of developmental processes that lead to short range patterns: patterns with a typical length scale of one cell (e.g. alternating patterns of cell fates or sharp boundaries between regions of cells). In animals, many of these patterns rely on the Notch signaling pathway which is the canonical communication system between neighboring cells. We use quantitative time lapse microscopy of mammalian cells together with mathematical modeling to study how the properties of the Notch signaling pathway affect pattern formation. We find that the Notch signaling pathway is designed to generate a switch between two mutually exclusive signaling modes: a ‘sender’ and a ‘receiver’. We show that this switch plays an important role in the differentiation of neighboring cells into distinct fates in several developmental patterning processes.

December 29th 2010: Yuval Garini (BIU)
Organization mechanisms of the genome in the nucleus studied through telomeres and DNA diffusion

The human genome contains tenth of thousands of genes that are organized in chromosomes and packed in the nucleus of the cell. How can the chromosomes and DNA stay organized in territories without any compartmentalization, while maintaining an unknotted order? This order is sustained throughout the life cycle of a cell, a property that emerges as a key contributor to genome function, though its full extent is not yet known.

Various approaches are used to address this question. We will discuss some of the methods.

We will describe the capability to shade light on the subject based on the study of the diffusion of various nucleus organelles such as telomeres and centromeres in vivo.

Methods for analyzing the diffusion pattern will also be described. We will also describe single molecule studies based on tethered particle motion to study the conformation properties of DNA, its interaction with proteins and its relevance to the maintenance of the genome order.

January 12th 2011: Shlomi Reuveni (TAU)
From the fractal-like nature of proteins to a mapping between thermal vibrations and random walk

Proteins are large organic molecules that play a vital role in all biological organisms. Fractals are geometrical objects that possess self-similarity. Recent studies have shown that proteins resemble fractals. This observation allowed us to harness the vast mathematical and physical machinery, originally developed during the study of ideal fractal systems, in order to quantitatively analyze protein structure and dynamics.

Quite unexpectedly, while studying proteins, we have also deepened our understanding of the relations between thermal vibrations of elastic networks and random walk on these networks. In particular we have shown that the solution for the mean first passage time problem on fractals is readily obtained using an analysis of thermal vibrations.

I will survey the work we have done in the past few years. Prior knowledge on proteins/fractals/random walk will not be assumed.

March 9th 2011: Moshe Gottlieb (BGU)
Block Copolymers at the Water-Oil Interface

The interfacial activity of amphiphilic block copolymers plays a significant role in industrial applications and processes and in biological systems. The main goal of the present work is to examine the relation between the structural properties of the polymers and their interfacial activity as reflected by surface pressure and interfacial rheology. The effect of the hydrophobic/hydrophilic blocks sizes ratio on the interfacial behavior was investigated along with the effect of the polymers architecture (diblock vs. triblock copolymers, ABA vs. BAB). The reduction of the interfacial tension and the interfacial dilatational rheology modulus were examined by using pendant drop apparatus combined with pulsating drop module. Interfacial shear rheology was determined by means of the magnetic needle and double ring methods. The information obtained by the different methods correlated with the conformation of the polymers at the interface allowing design of optimal polymeric surfactants.

March 23rd 2011: Yariv Kafri (Technion)
Target Location on DNA

Genomic expression depends critically both on the ability of (typical) regulatory proteins to locate specific target sites on a DNA within seconds and on the formation of long lived (many minutes) complexes between these proteins and the DNA. In the talk I will focus on the challenges posed on this process by the interactions between transcription factors and the DNA. First, I will present a possible classification of transcription factors according to their interaction energies (weight matrices) with the DNA. The classification will be illustrated using experimental data. I will then argue that each class calls for a different search process and will discuss the possible application of previously suggested mechanisms to each class. The talk will end with a new proposed mechanism which is based on barrier discrimination. It will be shown that this mechanism applies to all classes of transcription factors and can lead to a fast and specific search. Moreover, it is shown that the mechanism has interesting transient features which allow for stability at the target despite a rapid binding and unbinding of the transcription factor from the target.

April 6th 2011: Rony Granek (BGU)
Undulations and Dynamic Structure Factor of Membranes surrounded by viscoelastic continuous media

In this talk I will first review the so-called "Zilman-Granek theory" for membrane dynamic structure factor in case of an embedding purely viscous solvent. I will derive the dispersion relation of a nearly flat membrane, namely the relaxation rate of a single membrane bending mode of wavenumber q. I will show how this relation leads to the anomalous subdiffusion of a membrane segment in the transverse direction with a mean square displacement (MSD) evolving as ~t^2/3. In addition, the anomalous diffusion will be derived using a scaling hypothesis. I will then show how this anomalous diffusion leads to a stretched exponential decay of the dynamic structure factor of membrane phases at large wavenumbers k, S(k,t)~exp[(-Gamma_k*t)^2/3], with a relaxation rate Gamma_k that scales as ~kappa^(-1/2)*k^3, where kappa is the membrane bending modulus. A complementary scaling hypothesis will be used to derive the relaxation rate. I will briefly discuss a few experimental examples from the last decade.

Next I will generalize the dynamics to the case of a membrane surrounded by two semi-infinite viscoelastic fluids. By modeling the surrounding fluids as continuous media with frequency dependent shear modulii, G_1(omega) and G_2(omega), I will derive the dispersion relation for undulations. I will deduce the frequency-dependent transverse mean square displacement of a membrane segment and show that it is proportional to
kappa^(-1/3)*(G_1(omega)+G_1(omega))^(-2/3). I will then consider the linear response of a membrane to external forces. Possible implications will be elucidated: (i) for experiments probing the viscoelasticity of cells and vesicles encapsulating and/or embedded in viscoelastic fluids, (ii) for the dynamic structure factor of such systems, and (iii) for lamellipodia dynamics.

April 27th 2011: Oded Farago (BGU)
Entropy Driven Aggregation of Adhesion Sites of Supported Membranes

Supported lipid membranes are useful and important model systems for studying cell membrane properties and membrane mediated processes. One attractive application of supported membranes is the design of phantom cells exhibiting well defined adhesive properties and receptor densities. Adhesion of membranes may be achieved by specific and non-specific interactions, and typically requires the clustering of many adhesion bonds into ``adhesion zones''. One potential mediator of the early stages of the aggregation process is the Casimir-type forces between adhesion sites induced by the membrane thermal fluctuations. In the talk, I will present a theoretical analysis of fluctuation induced aggregation of adhesion sites in supported membranes. I will first discuss the influence of a single attachment point on the spectrum of membrane thermal fluctuations, from which the free energy cost of the attachment point will be deduced. I will then analyze the problem of a supported membrane with two adhesion points. Using scaling arguments and Monte Carlo simulations I will demonstrate that two adhesion points attract each other via an infinitely long range effective potential that grows logarithmically with the pair distance. Finally, I will discuss the many-body nature of the fluctuation induced interactions. I will show that while these interactions alone are not sufficient to allow the formation of aggregation clusters, they greatly reduce the strength of the residual interactions required to facilitate cluster formation. Specifically, for adhesion molecules interacting via a short range attractive potential, the strength of the direct interactions required for aggregation is reduced by about a factor of two to below the thermal energy kT

May 11th 2011: Benjamin Friedrich (WIS)
How active processes drive cytoskeletal order in living cells


June 21st 2011: Seth Fraden (Brandeis University)
Active Emulsions

Many phenomena of biological importance involve synchronization of oscillatory components. We explore here, in several geometries, the behavior of diffusively coupled, nanoliter volume, aqueous drops containing the reactants of the oscillatory Belousov-Zhabotinsky (BZ) reaction. A variety of synchronous regimes are found, including in- and anti-phase oscillations, stationary Turing patterns, and more complex combinations of stationary and oscillatory BZ-drops. A differential equation model based on a simplified description of the BZ chemistry and diffusion of messenger species reproduces a number of the experimental results. Materials science applications and possibilities for a chemical computer are discussed.