workshop-2011-02-24 -- Activities of LSCP

Protein Folding and Aggregation: Competition Reactions between Self-stabilization and Diffusion Limited Aggregation in Solution

Protein folding competes with intermolecular aggregation frequently. Understanding the mechanism underlying aggregate formation is required for the development of a wide variety of protein science. However, protein folding may follow a spontaneous process/off-path or an on-path folding process. This difference may be caused by the variant folding transition boundaries of interactions between protein and its folding environments. In this study both experimental study and molecular simulations indicated that an off-path refolding process of a reduced/unfolded growth hormone (GH) may contain a combination of a competition reaction of spontaneous folding and aggregation. Meanwhile, flat hexagonal plate aggregates of growth hormone molecules which is similar to one of the ice crystals, had been observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Combining with the random walk simulation and experimental observation, we may conclude that the mechanism of protein aggregation may via the diffusion limited aggregation (DLA) process.


Date :	24-26 February 2011
Place :	24-26 February: The auditorium on 1st floor, Institute of Physics, Academia Sinica, Taipei
Organized by :	National Center for Theoretical Sciences (Critical Phenomena and Complex Systems focus group) Institute of Physics, Academia Sinica (Taipei)
Contact Info. :	Miss Chia-Chi Liu (Secretary, Physics Division, NCTS) Tel:(886)-2-33665566; Fax:(886)-2-33665565; E-mail: ccliu@phys.ntu.edu.tw
Speakers :
	Porf. Chia-Ching Chang Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, TAIWAN E-mail:ccchang01@mail.nctu.edu.tw
		Protein Folding and Aggregation: Competition Reactions between Self-stabilization and Diffusion Limited Aggregation in Solution Protein folding competes with intermolecular aggregation frequently. Understanding the mechanism underlying aggregate formation is required for the development of a wide variety of protein science. However, protein folding may follow a spontaneous process/off-path or an on-path folding process. This difference may be caused by the variant folding transition boundaries of interactions between protein and its folding environments. In this study both experimental study and molecular simulations indicated that an off-path refolding process of a reduced/unfolded growth hormone (GH) may contain a combination of a competition reaction of spontaneous folding and aggregation. Meanwhile, flat hexagonal plate aggregates of growth hormone molecules which is similar to one of the ice crystals, had been observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). Combining with the random walk simulation and experimental observation, we may conclude that the mechanism of protein aggregation may via the diffusion limited aggregation (DLA) process.
	Miss Chun Ling Chang　 Institute of Physics, Academia Sinica, TAIWAN E-mail:clchang@phys.sinica.edu.tw
		Melting of DNA with Interstrand Crosslinks
	Mr. Hsin-Lin Chiang　 Institute of Physics, Academia Sinica, TAIWAN E-mail:jiangsl@phys.sinica.edu.tw
		Protein Aggregation in Silico
	Prof. Masao Doi Department of Applied Physics, the University of Tokyo, JAPAN E-mail: doi@rheo.t.u-tokyo.ac.jp
		Series of Lectures on Soft Matter Physics Soft matter (polymers, colloids, liquid crystals and surfactants) is an important class of materials in modern technology. It is also the base of future technology, i.e., medical and environmental applications. Yet, not much attention has been paid to soft matter in the conventional condensed matter physics:it is not taught in the usual curriculum of physics or material science. The purpose of this lecture is to provide a overview of soft matter for the undergraduate and graduate course students. Main target of this lecture is the students of physics and material science who have learned statistical mechanics, and started to learn condensed matter physics (which, conventionally, has been limited to solid state physics). The book intends to provide an introduction of soft matter (what they are, what are their characteristics) and also to provide advanced topics of statistical mechanics through various examples in soft matter: this includes, the concept of coarse graining and scaling, phase separation, order-disorder transition, Brownian motion, linear and non-linear responses etc).
	Porf. Keng-hui Lin　 Institute of Physics, Academia Sinica, TAIWAN E-mail:khlin@phys.sinica.edu.tw
		Morphology and Organization of Tissue Cells in 3D Ordered Cellular Solids The inverted colloidal crystal (ICC) has been suggested an ideal three-dimensional scaffold for cell cultures because of its uniform pore size and regular interconnectivity. We demonstrate a simple method to fabricate scaffolds of ICC geometry with tunable solid fraction and pore size. This process involves generating monodisperse liquid foam with a flow-focusing microfluidic device. The monodisperse liquid foam was further processed into open-cell solid foam, which was used as tissue-engineering scaffolds for cell culture. Three distinct cell types were cultured under these conditions and displayed appropriate physiological, morphological, and functional characteristics. Epithelial cells formed cyst-like structures and were polarized inside pores, myoblasts adopted a tubular structure and fused into myotubes, and fibroblasts exhibited wide varieties of morphologies depending on their location inside the scaffolds. The cellular behaviors inside the scaffolds are rich and the scaffolds fabricated by the microfluidic method can provide a platform to study 3D cell biology.
	Porf. Shinn-Zong Lin Neurosurgery, China Medical University Hospital, TAIWAN E-mail:shinnzong@yahoo.com.tw
		Genetically Modified Stem Cell Therapy Could Cure the Protein Aggregated Neurodegenerative Disease?
	Porf. C.-Y. David Lu Department of Chemistry, National Taiwan University, TAIWAN E-mail:cydlu@ntu.edu.tw
		The Shape Dynamics of the Multilamellar Vesicles Multi-lamellar vesicles (MLV) have an onion-like structure, where the concentric bilayer vesicles are nested to form a multilayer vesicle. Such MLV structure can arise as the thermodynamic stable phase, or be produced from lamellar phase as the metastable defect structure by external forcing, like the external electric field, high power sonication perturbation, or applied shear flow. It was reported that the (metastable) MLV produced by the shear flow has surprisingly monodisperse size distribution. Several theories in the literatures for the size-shear rate relation are based on the G.I. Taylor’s idea where the droplet elastic force is balanced by the viscous force. However, the connection between such scaling argument and the complicated MLV structure is vague, so that it is unclear of which theory is correct. Here we analyze the shape dynamics of the MLV, where the characteristic relaxation rates of MLV are calculated. The membrane interaction combined with the bilayer elasticity is balanced by the dissipation which is mainly the solvent flow between the neighboring bilayers of the MLV. Our analysis involves solving the creeping flow field between the neighboring bilayers, and applying the force balance on each bilayer. We find that the slowest mode emerged has accidentally the same scaling as the Taylor’s scaling form, which was previously used to interpret the experimental result. We also compare our result with the two different limiting cases: the well aligned flat lamellar dynamics, and the single layer vesicle dynamics. Our result agrees fully with the two limiting cases. As both cases are previously studied by the (light and neutron respectively) scattering experiments where the theoretical models fit well, it will be interesting to further study the MLV dynamics by scattering experiment.
	Porf. Chung-Yuan Mou Department of Chemistry, National Taiwan University, TAIWAN E-mail:cymou.ntu@gmail.com
		Nucleation in Protein Crystallization and Biomineralization Protein crystallization is the bottle-neck in structural biology in post-genomics era. Only one quarter of the protein could be solved for its 3D structure due to our lack ability to form good protein crystal. Biomineralization of bones, teeth and sea-shells are difficult problem lacking fundamental understandings. Crystallization of protein, biominerals and colloids follow the so-called non-classical crystallization process. The mesoscopic size of the crystallization unit makes them follow a two-step nucleation process: first a liquid-liquid separation process and then oriented attachment step. By this two-step crystallization, the free energy barrier for the total crystallization process can be reduced. Experimental examples in protein, Biominerals and colloids will be discussed.
	Dr. Karen Petrosyan Institute of Physics, Academia Sinica, TAIWAN E-mail: pkaren@phys.sinica.edu.tw
		1. Protein-Mediated Loops and Phase Transition in Nonthermal Denaturation of DNA We use a statistical mechanical model to study nonthermal denaturation of DNA in the presence of protein-mediated loops. We find that looping proteins which randomly link DNA bases located at a distance along the chain could cause a first-order phase transition. We estimate the denaturation transition time near the phase transition, which can be compared with experimental data. The model describes the formation of multiple loops via dynamical (fluctuational) linking between looping proteins, which is essential in many cellular biological process. 　 2.Stochastic Differential Equations for Modeling Biophysical Systems We apply the Poisson representation approach to various biophysical models described by the master equation. The method allows for derivation of stochastic differential equations with exact diffusion matrices without the system size expansion approximation. We consider applications of the method to biological systems which range from ecology and epidemiology to molecular evolution. Using the Poisson representation technique we were able to derive the equations for several models exactly and then via linearization around steady states obtain spectra for temporal and spatiotemporal fluctuations. Specifically, we have calculated spatiotemporal spectra for two stochastic spatiotemporal ecological models. For a stochastic predator-prey model the spectra confirmed the existence of quasicycles and the absence of spatial patterns. The stochastic Levin-Segel model was treated analytically with higher accuracy. For the case of epidemiological system we demonstrated the transformation of an individual level model described by master equation to stochastic equations that are exactly equivalent to that and then obtained the fluctuation spectrum. We underline that the method allows to study epidemiological models in cases of random and time-modulated environments.
	Porf. David B.Saakian Yerevan Physics Institute, Yerevan, Armenia E-mail:saakian@phys.sinica.edu.tw
		Some Exact Results for the Dynamic of the Chemical Master Equation We consider the chemical master equation with one-step processes. We derive exact dynamic, including explicit formulas for the variance of distribution, when the rates don't vary with the time. We found exact dynamics for the changing rates as well.
	Porf. Kiwing To Institute of Physics, Academia Sinica, TAIWAN E-mail:ericto@gate.sinica.edu.tw
		Mixing Dynamics of Slurry in Rotating Drum We study the effects of interstitial fluid viscosity on the rates of dynamical processes in a thin rotating drum half-filled with monodisperse glass beads. The rotating speed is fixed at the rolling regime such that a continuously flowing layer of beads persists at the free surface. While the characteristic speed of a bead in the flowing layer decreases with the fluid viscosity, the mixing rate of the beads is found to increase with the fluid viscosity. These findings are consistent to a simple model related to the thickness of the flowing layer.
	Prof. Zicong Zhou Department of Physics, Tamkang University, Taipei, TAIWAN E-mail: zzhou@mail.tku.edu.tw
		Stability of a Helical Semiflexible Biopolymer Confined in a Cylinder We study the stability of the helical configuration of an intrinsically-straight semiflexible biopolymer confined inside a cylindrical bacterium. We show that in fact the distributed (i.e., arclength dependent) force and torque are irrelevant in forming a perfect helix. We find that to have a stable helix of interesting, the biopolymer must be confined on the inner surface of the cylinder. We show that without excluded volume effect (EVE), a helix under compressive force is essentially unstable. With EVE, the helix becomes stable and may collapse into a ring-like configuration under compressive force. In contrast, torque disfavors the sharp change in extension. Our findings agree with the experimental observations for the MreB filament in a rod-shaped bacterium, and suggest that the EVE plays key role for the behavior of MreB inside bacterium.