Schedule of the Assembly and Self-Assembly at the Interface of Biology, Chemistry and Physics Conference

Living beings often produce remarkable structures, such as the silica shells of diatoma, or the sophisticated structures of striated muscles. One major current problem is to invent useful objects inspired by these structures, but simpler, and able to be produced in short times. Some examples will be presented. "Subtleties and Differences in the Interactions of Biological and Non-Biological Molecules and Surfaces" J. Israelachvili, University of California at Santa Barbara; Santa Barbara, USA Abstract: Recent SFA, AFM, Optical Trapping, and other measurements of the interactions and forces between biological surfaces and molecules show that these forces can be much more complex than expected from simple two-body interaction theories, such as the DLVO theory. Biological interactions differ from classic colloidal interactions in many ways: a biological interaction is generally a ‘process’ involving a sequence of individual two-body interactions that progress in a well-orchestrated fashion in both space and time. Thus, a binding event at one place can have an effect or trigger another interaction somewhere else (spatial dependence), and non-equilibrium, rate-dependent and time effects often play a crucial role (temporal dependence). The elemental interactions that make up a biological process are typically a mixture of short-range and longrange forces, specific and non-specific, and each one depends on different factors. These different interactions and the factors that affect them will be reviewed, with examples given of how they combine in such biological processes as membrane adhesion and fusion, recognition interactions, and transport. Recent SFA, AFM, Optical Trapping, and other measurements of the interactions and forces between biological surfaces and molecules show that these forces can be much more complex than expected from simple two-body interaction theories, such as the DLVO theory. Biological interactions differ from classic colloidal interactions in many ways: a biological interaction is generally a ‘process’ involving a sequence of individual two-body interactions that progress in a well-orchestrated fashion in both space and time. Thus, a binding event at one place can have an effect or trigger another interaction somewhere else (spatial dependence), and non-equilibrium, rate-dependent and time effects often play a crucial role (temporal dependence). The elemental interactions that make up a biological process are typically a mixture of short-range and longrange forces, specific and non-specific, and each one depends on different factors. These different interactions and the factors that affect them will be reviewed, with examples given of how they combine in such biological processes as membrane adhesion and fusion, recognition interactions, and transport. D. Leckband and J. Israelachvili “Intermolecular Forces in Biology” Quart. Revs Biophys. (in press) • Nonlinear Pattern Formation in Cell Biology “Cell Biology and Nonlinear Dynamics” E. Bodenschatz, Cornell University; Ithaca, USA Abstract: Many eukaryotic cells show a chemotactic response to spatio-temporal chemical gradients. Examples range from unicellular organisms to human cells involved in the immune system. In contrast to bacterial chemotaxis, eukaryotes do not need to move to sense a chemical gradient. Many eukaryotic cells show a chemotactic response to spatio-temporal chemical gradients. Examples range from unicellular organisms to human cells involved in the immune system. In contrast to bacterial chemotaxis, eukaryotes do not need to move to sense a chemical gradient. The cell membrane is homogenously covered by receptors and cell sizes can be small (10 microns). The questions are: How do cells detect chemical gradients? What are the cellular processes that are needed for polarization? One prototype system for cellular development and chemotaxis is the social amoeba Dictyostelium discoideum (dicty). It is believed that dicty has similar molecular networks for chemotaxis as other eukaryotic cells. Upon starvation, dicty turns on a sophisticated genetic program during which cells develop a chemical relay system involving the detection, production and release of cyclic AMP (cAMP). This relay process creates a pattern of macroscopic spiral waves, which chemotactically guide the cells towards aggregation centers. Subsequently cells differentiate, a migrating slug is formed, and this multicellular part of the life cycle ends with the development of a fruiting body. Thus, chemotaxis to traveling concentration waves plays an indispensable role in dicty biology. Dicty is well suited for the study of this capability since a large number of cells can be developed simultaneously and reproducibly. In addition, a library of strains with GFP-fused proteins is available for the optical study of intracellular and extra cellular dynamics. It has been experimentally shown that the chemotactic response of dicty to a gradient of cAMP requires translocation of the cytosolic protein CRAC to the cell membrane. A release of cAMP from a pipette elicits a translocation of CRAC to the nearside of the cell. Later the cell extends pseudopods towards this direction and moves up the gradient. In this talk, we will first review existing experimental results on dicty chemotaxis. Then, we will present a model that could explain the observed behavior, especially the very rapid response timescale. Finally, we will discuss planned experiments, which will both test this specific model and which will provide more a quantitative characterization of the decisionmaking steps in this process. The work is conducted in collaboration between Cornell U. (I. Rafols, T. Tanaka, E.B.) and the University of California at San Diego (W.Rappel, P.Thomas, H. Levine, Bill Loomis). We gratefully acknowledge support by the NSF-Biocomplexity program. “Intracellular Pattern Formation Based on the Actin System” G. Gerisch, Max-Planck-Institute for Biochemistry; Munich, Germany Abstract: Amoeboid cells like those of Dictyostelium have no stable polarity, but in order to move persistently they have to polarize into a leading edge and a tail. This establishment of cellular organization occurs in a quasi-periodic fashion and is based on supramolecular structures formed by the cytoskeleton, primarily by the actin system. Actin exists in an equilibrium between monomeric G-actin and filamentous polymers (F-Actin). A large variety of actin-binding proteins determines this equilibrium and controls the assembly of actin filaments into higher-order structures. In fast moving cells like neutrophils or Dictyostelium cells the actin system is highly dynamic; reorganization occurs within a few seconds either spontaneously or in response to external signals. The role of actin-binding proteins in promoting this reorganization is being determined by physical methods under defined conditions in vitro as well as by genetic manipulation in the context of the living cell. The modeling of these data on single proteins into a network of macromolecular interactions will be a challenge for theoretical studies. Amoeboid cells like those of Dictyostelium have no stable polarity, but in order to move persistently they have to polarize into a leading edge and a tail. This establishment of cellular organization occurs in a quasi-periodic fashion and is based on supramolecular structures formed by the cytoskeleton, primarily by the actin system. Actin exists in an equilibrium between monomeric G-actin and filamentous polymers (F-Actin). A large variety of actin-binding proteins determines this equilibrium and controls the assembly of actin filaments into higher-order structures. In fast moving cells like neutrophils or Dictyostelium cells the actin system is highly dynamic; reorganization occurs within a few seconds either spontaneously or in response to external signals. The role of actin-binding proteins in promoting this reorganization is being determined by physical methods under defined conditions in vitro as well as by genetic manipulation in the context of the living cell. The modeling of these data on single proteins into a network of macromolecular interactions will be a challenge for theoretical studies. A highly sophisticated organization of the cytoskeleton is required for cell division, a process in which segregation of the chromosomes is coordinated in space and time with the formation of a cleavage furrow separating the daughter nuclei. Mutant cells of Dictyostelium lacking the conventional double-headed myosin II proved to be an excellent system to study patterning of the cell cortex into polar regions and a cleavage furrow. These myosin II-null cells are unable to divide in suspension, thus becoming multinucleate. When brought into contact with a solid surface, cells are even in the absence of myosin II capable of dividing by the formation of multiple cleavage furrows. This process is preceded by the sorting out of actinbinding proteins, in the same way as it occurs in normal cells undergoing bipartite division. By tagging relevant proteins with green fluorescent protein (GFP), this protein sorting can be recorded in vivo. Examples analyzed are coronin, a protein enriched at the polar regions of a dividing cell, and cortexillin, which accumulates in the cleavage furrow. Elimination of each of these proteins by targeted gene disruption has shown that both contribute to proper cell division. Gerisch, G. and Weber, I. (2000). Cytokinesis without myosin II. Review. Curr. Opin. Cell Biol. 12, 126-132. Neujahr, R., Albrecht, R., Köhler, J., Matzner, M., Schwartz, J.-M., Westphal, M. and Gerisch, G. (1998). Microtubule-medaited centrosome motility and the positioning of cleavage furrows in multinucleate myosin II-null cells. J. Cell Sci. 111, 1227-1240. Weber, I., Gerisch, G., Heizer, C., Murphy, J., Badelt, K., Stock, A., Schwartz, J.-M. and Faix, J. (1999). Cytokinesis mediated through the recruitment of cortexillins into the cleavage furrow. EMBO J. 18, 586-594.