Research in Biophysics, Soft Materials and Pattern Formation

The soft matter and biophysics group started at LCE in September 2000. In general, the research is geared towards the interface between condensed matter physics, biology and material science. The great diversity of these systems, ranging, for instance, from complexes of DNA and cationic liposomes used in gene transfer to unexpected morphological evolution of polymers under shear flow and to pattern formation in biological processes, provides new challenges in both fundamental and applied research.

Typically, biological processes take place under non-equilibrium conditions. Modeling these processes provides many theoretical challenges since eventually the validity of equilibrium concepts, such as universality and scaling laws, breaks down. It is important to study their range of validity, and how the emergence of new time and length scales, and possibly a steady state, is manifested in dynamical systems. A good example of that is the shear flow behavior of complex fluids where the dynamics of order-disorder transition depends intimately on the application of shear. As vast number of industrial processes involve complex fluids and polymer mixtures under shear flow conditions, it is clear that a better theoretical understanding of these processes has immediate practical applications.

Another challenge arises from the interdisciplinary nature of these problems. A strong interaction between theory, computation, and experiments is essential in order to get insight of into the physical mechanisms producing these complex, often collective, phenomena. A clear example of this is the study of lipoplexes, i.e., the formation and behavior of DNA-cationic liposome complexes. There exists a large amount of experimental data, and in vivo experiments have shown that clinical application of lipoplexes is effective and safe. However, the processes and physical mechanisms, e.g., those involving interactions of electrostatic origin, that control the formation of these complex structures are not well established. Theoretical studies and, in particular, simulational studies, have the potential of helping to characterize better these complex processes.

The studies introduced below briefly describe our efforts in soft matter and biophysics. For details and up-to-date information, please see the corresponding project home page as given in connection of each project.

The group has been very active during its young life and at the end 2003 the Biological Physics Team consisting of our group together with Dr. Ilpo Vattulainen’s group at the Laboratory of Physics was selected as a Helsinki University of Technology Young Center of Excellence for 2004-2005 (in Finnish: tutkimuksen kärkiryhmä).


Sterol Interaction with Membrane Lipis

Researchers: Tomasz Róg, Ilpo Vattulainen* and Mikko Karttunen
*Laboratory of Physics and Helsinki Institute of Physics, HUT

Cholesterol (Chol) is an important constituent of eukaryotic cell membranes where it accounts for up to 50 mol% of the membrane lipids. The biological roles of Chol involve maintenance of proper fluidity, formation of glyco-sphingolipid-Chol-enriched raft domains, reduction of passive permeability, and increasing the mechanical strength of the membrane. The Chol molecule consists of a planar tetracyclic ring system with the 3-hydroxyl group and a short 8-carbon atom chain. The planar tetracyclic ring system of Chol is not symmetric about the ring plane. The sterol ring has a flat side with no substituents ( -face) and a rough side with two methyl substituents ( -face). In natural and model membranes, Chol effectively increases the order of saturated alkyl chains of phospholipids (ordering effect) and the membrane surface density (condensing effect). Chol analogues, whose molecular structures often differ little from that of Chol, affect membrane ordering and condensation much less. Thus, the molecular structure of Chol seems to be optimal for its biological membrane functions. The main goal of these studies has been to elucidate the relationship between the Chol structure and its effect on the bilayer made of saturated and unsaturated PC molecules. In this aim six model of lipid bilayers were constructed - three composed of DPPC (dipalmitoylphosphatidylcholine), and three of DOPC (dioleoylphosphatidylcholine). To the pure PC bilayer cholesterol and modified cholesterol were added. 100 ns of the molecular dynamics simulation of these systems were performed using GROMACS software. In the modified cholesterol molecules both methyl substituents were removed from the -face, so the molecule has two flat faces. Analyses of obtained trajectories will provide information about the role of and -faces of cholesterol as well as help as understand the evolutionary pathway of sterol family on which we observed removal of methyl group.

General Anaesthesia and Cellular Membranes

Researchers: Lorna M. Stimson, Mikko Karttunen, Tomasz Róg and Ilpo Vattulainen*
*Laboratory of Physics and Helsinki Institute of Physics, HUT

Molecular dynamics simulations of fully hydrated lipid bilayers exposed to an anaesthetic gas are the first step towards the justification of the hypothesis that the key to the mechanism of some anaesthetics lies not in their interaction with binding sites, but in the effect that they have on the cell membrane. Such simulations allow an understanding of the structural and dynamic modifications that are necessary to accommodate the anaesthetic molecules within the bilayer. This information may then be used to impose similar environmental influences on integral proteins embedded within a model membrane. These changes to the nanopores or channels in the membrane have a number of repercussions such as to modify the efficiency of ion diffusion through the bilayer. In turn such affects may control the potential across the membrane. This voltage across the bilayer is essential for nerve impulses to be conducted along a neuron. Hence, modifications in the lipid bilayer can be directly related to anaesthetic effects.

At present the simulations involved in this work are conducted using GROMACS software. The systems under investigation involve 128 lipid molecules in a bilayer surrounded by solvent water molecules. The lipid bilayers being investigated are dipalmitoylphosphatidylcholine, dioleoylphosphatidylcholine and combinations of each of those with cholesterol. For each bilayer a number of different simulations with different concentrations of anaesthetic gas are considered and the effect on the membrane is quantified by measurable quantities such as the geometric conformation of parts of the system, the lateral pressure profile, order parameters, the area per lipid and radial distribution functions. These properties can help in the formation of a description of the local environment of a protein in a cell membrane under various conditions.

Figure 23

Figure 23: Simulation snapshot illustating the accomodation of xenon gas in the cell membrane

Computer Simulations of a Polymer Chain under Shear Flow

Researchers: Markus Miettinen, Mikko Karttunen, Michael Patra and Ilpo Vattulainen*
*Laboratory of Physics and Helsinki Institute of Physics, HUT

Project home page: http://www.lce.hut.fi/research/polymer/

The effect of shear flow on rhelogical properties of polymer mixtures is of great interest because the nonequilibrium nature of the problem makes it theoretically and computationally difficult. On the other hand, looking from the practical point of view, industrial processes often involve polymer mixtures under shear flow. A better theoretical knowledge of how to, e.g., control viscosity and phase separation would have immediate consequences in developing more efficient processes.

Dissolved polymer chains are known to undergo a globule to open coil transition as the solvent quality changes from poor to good. Likewise, it has been found out that an individual polymer chain undergoes a collapsing – stretching behaviour when the solute is exposed to shear. In this study, we look into the combined effect of shear flow and solvent properties to the conformational changes of the polymer chain.

The first part of the study has concentrated on the effect of solvent quality, i.e., studying the properties of a freely floating chain as a function of solubility. This offers a sturdy reference for the second part, which will introduce applying shear to the system. The chain properties will be measured as a function of both the shear strength and the solvent quality.

The solvent is modeled explicitly by monomers interacting with each other through a Lennard-Jones -type (LJ) potential. The polymer model is made up of a few dozen LJmonomers freely jointed together by nonlinear FENE-springs. The first part of the study will be performed by carrying out Molecular Dynamics (MD) simulations in three dimensions, changing the solvent properties by modifying the interaction coefficients of the LJ-potential. The second part shall consist of Nonequilibrium Molecular Dynamics (NEMD) simulations using the SLLOD algorithm with Lees-Edwards boundary conditions for implementing the shear.

Figure 24

Figure 24: Stretching and collapsing of a single molecule under shear flow.

Dissipative Particle Dynamics Studies of Coarse-grained Polymer Systems

Researchers: Petri Nikunen, Mikko Karttunen, and Ilpo Vattulainen*
*Laboratory of Physics and Helsinki Institute of Physics, HUT

Project home page: http://www.softsimu.org/

The physics of polymeric liquids has been a problem of considerable interest in recent years. From a modeling point of view, these systems are problematic due to the fact that numerous phenomena take place at mesoscopic time and length scales, which are not accessible by detailed simulation techniques such as molecular dynamics. To overcome this problem, a number of “coarse-grained” approaches have been suggested and developed to simplify the underlying microscopic model without changing the essential physics.

One candidate to work with is the dissipative particle dynamics method. It is a particlebased simulation technique which suits particularly well for studies of soft condensed matter systems. Due to this, it has been applied to various systems, including the structure of lipid bilayers, self-assembly, and the formation of polymer-surfactant complexes. In our project, we concentrate on methodological aspects of this method, and apply it e.g. to vesicle formation (figure below).

Figure 25

Figure 25: Formation of a vesicle. Time goes from left to right, top row illustrating the vesicle from outside and bottom row from inside.


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