2014 Seminars

The problem of self reproduction: from bacteria to artificial cells
Albert Libchaber, The Rockefeller University
October 31, 2014, 4:00pm PAB 4-330

Abstract: Can we synthesize the most elementary cell size compartment that can self-reporduce using genetic information? We will discuss applying high hydrostatic pressure to E. coli bacterium during self reproduction. This is a reversible stress with controlled amplitude.



DNA confinement drives uncoating of the HIV Virus 
Robijn Bruinsma, UCLA Physics & Astronomy
October 17, 2014, 4:00pm, PAB 4-330

Abstract: The capsid that protects the genome molecule(s) of a virus is in general quite robust against mechanical stress. An outstanding exception is the mature capsid of retroviruses, such as HIV. We present a description of the mature HIV capsid where a key function is not the mechanical protection of the genome but instead a role as a "reactor vessel" for the action of the enzyme reverse transcriptase that converts single-stranded RNA molecules into double-stranded DNA molecules inside mature HIV viral capids. The uncoating of the HIV virus is determined by the fracture force exerted on the capsid wall by the DNA torus that is produced by the reverse transcriptase. 

The interaction between soft colloid particles and an immersed fibrous network
Louis Foucard, UCLA Chemistry & Biochemistry
October 3, 2014, 4:00pm, PAB 4-330

Many colloidal-sized particles encountered in biological and membrane based separation applications can be characterized as soft vesicles such as cells, yeast, viruses and surfactant micelles. The deformation of these vesicles are expected to critically affect permeation by accommodating pore shapes and sizes or enhancing the adhesion with a pore surface. Numerical and theoretical modelings of these processes will be critical to fully understand these processes and thus design novel filtration membranes that target, not only size, but deformability as a selection criterion.

This talk will introduce a multiscale strategy that enables the determination of the permeability of a fibrous network with respect to complex fluids loaded with vesicles. First, a particle-based moving interface method that can be used to characterized the severe deformation of vesicles interacting with an immersed fibrous network is introduced. Second, a homogenization strategy that permits the determination of a network permeability, based on the micromechanisms of vesicle deformation and permeation is presented.

As a proof of concept, the role of vesicle-solvent surface tension on the permeation of both solvent and vesicle through a simple 2D fiber network is investigated.

Pictured at left: Vesicle going through a fibrous network for different capillary numbers.





Elegant Mind Seminar: Exploring the origin of life and consciousness through the neural systems of C. elegans
Katsushi Arisaka, UCLA Physics & Astronomy
May 30, 2014, 3:00pm, Kinsey Teaching Pavilion 1200B

“Why are we here? What are we?”  

These fundamental questions, concerning the origin of life and consciousness, are investigated through behavioral analysis of the small nematode organism, C. elegans. The organism is fully sequenced, with an established connectome of 302 neurons. The dynamic functions of the nervous system, however, cannot be addressed from the connectome alone. It remains to be uncovered how these biologic functions are influenced by the environment for adaptation and learning. 100 students in lab focused on understanding such dynamic functions of the C. elegans nervous system, and studied how behavioral functions change through environmental interaction. Topics of study include 2D and 3D navigation under stimulations of E/B-fields, UV/visible lights, and temperature change. This talk presents the students’ findings of amazing and unexpected behaviors. Lastly, an ambitious plan is presented to advance the frontier of science concerning the origin of life and consciousness.

Also please feel free to attend the Elegant Mind Club at UCLA, open house May 30 12 noon to 5:00pm

Simple polymer models of proteins in the unfolded state:  A spherical cow?
Dmitrii E. Makarov, The University of Texas at Austin
May 23, 2014 4:00pm, PAB 4-330 

Contrary to the common misconception that biologically functional proteins always have to adopt well defined 3-dimensional shapes, at least 25% of proteins in our body are completely disordered and many more contain long unstructured segments. Being unstructured has a number of biological advantages and may, for example, speed up proteins’ search for their targets, facilitate protein degradation by the cell machinery, or impart remarkably high toughness to natural elastomeric materials (e.g. spider silk). For those proteins that are found folded under physiological conditions, the time it takes to attain their biologically active state is further controlled by the rate at which the unstructured polypeptide chain can explore its conformational space. 

In this talk, I will describe our efforts to develop very simple yet predictive polymer models of unfolded proteins.  Polymer theory predicts universal scaling laws governing disordered polymer chains, which hold regardless of chemical details as long as the chains in question are long enough. Real proteins, however, are often relatively short and so the use of simple polymer theories may (justifiably) be viewed as studying a spherical cow.  Nevertheless, I hope to convince the audience that rather simple models can quantitatively account for experimental measurements of unfolded proteins (particularly single-molecule FRET and “loop formation” studies) and agree well with arguably more realistic atomistic simulations.  In particular, I will describe recent experimental evidence for “internal friction” in protein dynamics and discuss the molecular origins of this effect. 

Elasticity on the edge of stability: soft matter inspired by the cell 

Fred MacKintosh, VU University, Amsterdam
April 9, 2014 9:00am, PAB 4-330 

Much like the bones in our bodies, the cytoskeleton consisting of stiff protein biopolymers determines the mechanical stability and response of cells. Unlike passive materials, however, living cells are kept far out of equilibrium by metabolic processes and energy-consuming molecular motors that generate forces to drive the machinery behind various cellular processes.

Inspired by such networks, we describe recent theoretical and experimental advances in our understanding of fiber networks in vitro and in vivo. We show that these exhibit a unique state of highly responsive matter near the isostatic point first studied by Maxwell.

For fiber networks, this represents a marginal state of matter with exceptional mechanical properties, including a strongly nonlinear elastic response and zero-temperature critical behavior. We discuss how this can help us to understand long-standing problems in tissue mechanics.  Moreover, the introduction of molecular motor activity can dramatically affect the stability of such systems. 

The Dynamics of Fibrin Gel Formation

James P. Keener, Ph.D., Distinguished Professor of Mathematics, Adjunct Professor of Bioengineering, University of Utah
March 27, 2014, 4:00pm, 13-105 Center for the Health Sciences (CHS)
Biogels are complex polymeric networks whose proper function is important to many physiological processes.  For example, the proper function of mucus gel is important for airway clearance, reproduction, digestion, gastric protection, and disease protection and its failure is involved in cystic fibrosis, gastric ulcers, and reproductive dysfunction.  Fibrin clots are crucial for prevention of bleeding after injury but inappropriate formation of clots is implicated in hearts attacks and strokes.
There are three phases of biogel dynamics that are important to their biological function.  These are their formation (i.e., blood clotting), degradation (clot dissolution), and swelling/deswelling kinetics (during mucin secretion/exocytosis, for example).
The purpose of this talk is to describe recent advances in the study of the dynamics of fibrin clot formation.  In particular, I will derive and discuss features of a new partial differential equation model that describes the growth of fibrin clots as a polymerization/gelation reaction.  The solution of this PDE model gives insight into the branching structure of clots that are formed under various physiological conditions.
Host: Tom Chou, Ph.D

Quantitative modeling of nucleic-acid protein interactions

Ralf Bundschuh, Ohio State University
March 14, 2014, 4:00pm - 5:00pm, 4-330 PAB 

The interactions of proteins with nucleic acids are fundamental for gene regulation.  We will discuss two aspects of these interactions where quantitative modeling provides novel insights into biological mechanisms.

The first is the binding of transcription factors to DNA. It is well known that nucleosomes reduce the affinity for transcription factors to binding sites covered by the nucleosome.  It has been assumed that this is due to a reduction in on-rate since a transcription factor can only bind when a rare thermal fluctuation of the nucleosome makes the DNA accessible.  However, recent experimental data surprisingly shows that 
the off-rate of transcription factors is also strongly affected in the presence of a nucleosome.  We demonstrate that this increase in off-rate by several orders of magnitude is a consequence of a competition between partial binding events of dimeric transcription factors and the nucleosome.

Second, we will investigate the interaction between proteins and RNA. Post-transcriptional regulation requires many proteins to bind to RNA. Implementation of combinatorial regulation requires cooperativity between such binding events.  In the case of single-stranded RNA binding proteins, a competition emerges between binding by proteins and formation of intramolecular base pairs of the RNA.  We show that this competition provides a natural mechanism for the required cooperativity between RNA binding proteins.

Polymer mechanics in bacteria - Growth, division, and morphogenesis

Jen Hsin, Stanford University
March 7, 2014, 4:00pm - 5:00pm, 4-330 PAB
Polymers assembled by proteins play essential roles in cell physiology.  In this talk I will present our works using realistic physics-based computations (molecular dynamics simulations), in combination with theoretical modeling, to reveal the physical mechanisms of polymers in key cellular processes such as division, growth, and maintaining the correct cell shape.  I will illustrate how a polymer converts chemical energy to mechanical energy, which provides the constrictive force needed for cell division to narrow cell width.  I will then discuss interactions between two polymers, and how their relative mechanical properties such as bending direction and stiffness can determine their cellular architectures.  Lastly, I will consider another major class of polymers that is made of inherently dynamic protein units, and explore the evolutionary significance of employing diverse polymer types to perform different cellular functions.

A physical model of cell-intercalation

Madhav Mani, KITP and UC Santa Barbara
February 28, 2014, 4:00pm - 5:00pm 4-330 PAB

The local rearrangement of cellular neighbors, termed cell-intercalation, results in the alteration of tissue shape and the emergent changes in embryonic form - morphogenesis. Despite our molecular understanding of how the cytoskeleton generates active stresses we lack a physical mechanism that underlies the rearrangement of cellular lattices, in particular accounting for their manifestly collective features. Relying on empirical analyses of live fluorescent microscopy of Drosophila Germ Band Extension (Lecuit Lab, Marseilles) our work makes three key advances: 1) construction of an image-analysis tool that allows a non-destructive measurement of relative tissue stresses, 2) insights into the physics of epithelial tissues that reveals the importance of shear stresses between cells and 3) accounting for the generic features of mechanical feedback on cytoskeletal levels. These ingredients are brought together into a simple mathematical model that provides insight into the observed local and global features of cell-intercalation and, more broadly speaking, into the dynamics of cellular lattices in a wide array of different tissues and animals.

Dynamics of Particles in Soft Matter

Michael Rubenstein, University of North Carolina
February 21, 2014, 4:00pm - 5:00pm

Abstract: Can the properties of materials be deduced from the analysis of the trajectories of probe particles diffusing through them? The anomalous diffusion of a particle in complex media could be due to three fundamental reasons: (1) Viscoelastic response of the medium to the deformation imposed on it by the moving particle; (2) The particle could be attracted to some regions of heterogeneous medium and be temporary localized in these "sticky" regions; (3) The particle is repelled from some regions of the medium and has to go over different energy barriers in order to diffuse through this medium. Can one determine which of these fundamental reasons cause the anomalous diffusion? We propose a method of analyzing particle trajectories to answer this question and to determine the corresponding properties of complex media such as distribution of relaxation times or energy distribution of attractive regions.

We solve activated hopping model in which particle experiences thermally activated jumps between neighboring wells of different energy depths. We find that the particle diffusion is ordinary Brownian (not anomalous) if the width of the distribution of well energies ΔU is smaller than thermal energy kT. In the opposite case (ΔU>kT) we discover the surprising result that although jumps between neighboring wells are completely random and uncorrelated, the particle displacements during consecutive time intervals are correlated. The source of these correlations is that the particle can be located in the same well during both time periods. As the result, while the mean square displacement of the particle is still Brownian, the distribution of displacements is non-Gaussian and is almost exponential. 

We use scaling theory to derive the time dependence of the mean-square displacement <r2(t)> of a probe nanoparticle in polymer solutions and melts. We distinguish several qualitatively different cases depending on the size d of the particle in comparison to solution correlation length ξ and tube diameter a for entangled polymer liquids. We also describe a hopping mechanism for diffusion of particles larger than mesh size of polymer solids (networks and gels).

Elasticity, Geometry, and Buckling

Andrj Kosmrlj, Harvard
February 14, 2014, 4:00pm - 5:00pm 4-330 PAB

Abstract: In this talk I present how geometrical shape affects the mechanical properties of thin solid membranes and how buckling instabilities change the geometry of periodic microstructures in materials. Using methods rooted in statistical physics, we find that random shape fluctuations and thermal excitations of thin solid membranes significantly modify their mechanical properties. Such membranes are much harder to bend, but easier to stretch, compress and shear. Finally, I show how methods from solid state physics can help us deduce the geometry of buckled periodic microstructures. Buckling instabilities can change the microstructure symmetries, including a spontaneous chiral symmetry breaking, which drastically modifies the material properties.


A Black Hole of Memory: Cytoskeletal Collapse in Late Stages of Alzheimer’s Disease? *

D.L. Cox, University of California, Davis
February 7, 2014, 4:00pm - 5:00pm

In the late stages of Alzheimer’s disease, the tau proteins that serve to nucleate, stabilize, and crosslink microtubules in the axons of nerve cells are degraded.  The customary view is that the removal of taus can allow for the catastrophic dynamical instability of microtubules in which depolymerization of tubulin monomers overwhelms polymerization and the microtubules vanish.  We offer an alternative perspective, that removal of taus essentially corresponds to a problem of rigidity percolation with the added feature of a depletion force induced by the taus themselves.  We show with a combination of 2D projected simulations and analytic arguments that there is an irreversible first order collapse when too many taus are removed, driven by the attractive depletion force, loosely analogous to gravitational collapse.  The values of tau density and entropic spring constants are such to make this likely dominate over the dynamic instability for a wide range of tau occupancies.  If correct, these arguments point to kinase phosphorylation as the main mechanism of tau degradation.   We discuss possible experimental tests of this on cultured neurons and whether “white matter” volume loss observed by functional MRI in afflicted patients can be attributed to this phenomenon.  Clearly this collapse represents a “Point of No Return” signpost in disease progression and therapeutic intervention. 

*Work supported by US NSF Grants DMR-1207624 and DMR-0844115 in collaboration with A. Sendek, H.R. Fuller, N.E. Hall, and R.R.P. Singh. 

Coupled Oscillators and Arnold Tongues in Cell Dynamics
Mogens H. Jensen, Niels Bohr Institute, Copenhagen, Denmark
January 21, 2014, 4:00pm - 5:00pm

Oscillating genetic patterns have been observed in networks related to the transcription factors NFkB, p53 and Hes1 [1]. We identify the central feed-back loops and found oscillations when time delays due to saturated degradation are present. By applying an external periodic signal, it is sometimes possible to lock the internal oscillation to the external signal. For the NF-kB systems in single cells we have observed that the two signals lock when the ration between the two frequencies is close to basic rational numbers [2]. The resulting response of the cell can be mapped out as Arnold tongues. When the tongues start to overlap we observe a chaotic dynamics of the concentration in NF-kB [2]. Oscillations in some genetic systems can be triggered by noise, i.e. a linearly stable system might oscillate due to a noise induced instability. By applying an external oscillating signal to such systems we predict that it is possible to distinguish a noise induced linear system from a system which oscillates via a limit cycle. In the first case Arnold tongues will
not appear, while in the second subharmonic mode-locking and Arnold tongues are likely [3].

[1] B. Mengel, A. Hunziker, L. Pedersen, A. Trusina, M.H. Jensen and S. Krishna, "Modeling oscillatory control in NF-kB, p53 and Wnt signaling", Current Opinion in Genetics and Development 20, 656-664 (2010).

[2] M.H. Jensen and S. Krishna, "Inducing phase-locking and chaos in cellular oscillators by modulating the driving stimuli", FEBS Letters 586, 1664-1668 (2012).

[3] N. Mitarai, U. Alon and M.H. Jensen, "Entrainment of linear and non-linear systems under noise", Chaos, 23, 023125 (2013).