Bulletin of the American Physical Society
2009 APS March Meeting
Volume 54, Number 1
Monday–Friday, March 16–20, 2009; Pittsburgh, Pennsylvania
Session L7: Mechanics of Biomolecular Systems I |
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Sponsoring Units: DBP Chair: Jens-Christian Meiners, University of Michigan Room: 407 |
Tuesday, March 17, 2009 2:30PM - 3:06PM |
L7.00001: First-principles Calculation Of DNA Looping In Tethered Particle Experiments Invited Speaker: We show how to calculate the probability of DNA loop formation mediated by regulatory proteins such as Lac repressor, using a mathematical model of DNA elasticity. Our approach has new features enabling us to compute quantities directly observable in Tethered Particle Motion (TPM) experiments; e.g. it accounts for all the entropic forces present in such experiments. Our model has no free parameters; it characterizes DNA elasticity using information obtained in other kinds of experiments. It can compute both the ``looping J factor'' (or equivalently, looping free energy) for various DNA construct geometries and repressor concentrations, as well as the detailed probability density function of bead excursions. We also show how to extract the same quantities from recent experimental data on tethered particle motion, and compare to our model's predictions. In particular, we present a new method to correct observed data for finite camera shutter time. The model successfully reproduces the detailed distributions of bead excursion, including their surprising three-peak structure, without any fit parameters and without invoking any alternative conformation of the repressor tetramer. However, for short DNA loops (around 95 bp) the experiments show more looping than is predicted by the linear-elasticity model, echoing other recent experimental results. Because the experiments we study are done in vitro, this anomalously high looping cannot be rationalized as resulting from the presence of DNA-bending proteins or other cellular machinery. We also show that it is unlikely to be the result of a hypothetical ``open'' conformation of the repressor.\\[4pt] Ref: KB Towles et al, accepted for publication in Physical Biology. [Preview Abstract] |
Tuesday, March 17, 2009 3:06PM - 3:42PM |
L7.00002: Modulation of membrane mechanical properties by Sar1, a vesicle trafficking protein. Invited Speaker: The trafficking of cargo in cells involves dramatic changes in membrane shape and topology. Though trafficking is widely studied and the identities and interactions of the responsible proteins are well mapped, remarkably little is known about the mechanics involved. We focus on Sar1, the key regulator of the coat protein complex II (COPII) family that ferries newly synthesized proteins from the ER to the Golgi. Sar1 is the only member of the COPII coat that interacts directly with the ER lipid bilayer membrane. It has an amphipathic N-terminal helix; when Sar1 is GTP-bound, the helix is exposed and the hydrophobic hemi-cylinder can insert into the bilayer. To investigate whether Sar1 has a role beyond merely localizing the other COPII proteins, we directly measure the force involved in membrane deformation as a function of its presence or absence, using optically trapped microspheres to pull tethers from lipid membranes whose composition and large surface area mimic the composition and geometry of the ER. Tether measurements allow extraction of the membrane bending modulus, the parameter that governs the energetics of deformation. We find that the bending modulus measured in the presence of Sar1 with a non-hydrolyzable GTP analogue is half that measured without Sar1 or with Sar1-GDP. These results reveal a paradigm-altering insight into COPII trafficking: Sar1 actively alters the material properties of the membranes it binds to, lowering the energetic cost of curvature generation. [Preview Abstract] |
Tuesday, March 17, 2009 3:42PM - 4:18PM |
L7.00003: ABSTRACT WITHDRAWN |
Tuesday, March 17, 2009 4:18PM - 4:54PM |
L7.00004: ``Double Bubble'' and other trouble with DNA looping Invited Speaker: DNA looping is essential for such biological processes as regulation of gene expression and DNA packaging into nucleosomes. Classical theory of looping, based on the elastic description of DNA, was proposed more than two decades ago by Shimada and Yamakawa. However, a number of puzzles related to the problem remain largely unresolved to date. For instance, DNA loops in nature tend to be significantly shorter than the optimal once predicted theoretically, and the looping probability appears to be much larger. Even in vitro experiments conflict with each other and with the theory. In my talk, I will review a number of mechanisms which may be responsible for these discrepancies, and which add complexity to the overall problem. I will briefly discuss possible roles of bending-induced and protein-induced structural defects (such as kinks and bubbles), as well as effects of boundary constraints. I will then focus on two phenomena: the effect of sequence disorder, and the loop formation in a supercoiled DNA. The former results in the lack of self-averaging of looping probabilities. The supercoiling may explain the smaller optimal loop size observed in vivo. [Preview Abstract] |
Tuesday, March 17, 2009 4:54PM - 5:30PM |
L7.00005: Push or Pull? -- Cryo-Electron Microscopy of Microtubule's Dynamic Instability and Its Roles in the Kinetochore Invited Speaker: Microtubule is a biopolymer made up of alpha-beta-tubulin heterodimers. The tubulin dimers assemble head-to-tail as protofilaments and about 13 protofilaments interact laterally to form a hollow cylindrical structure which is the microtubule. As the major cytoskeleton in all eukaryotic cells, microtubules have the intrinsic property to switch stochastically between growth and shrinkage phases, a phenomenon termed as their dynamic instability. Microtubule's dynamic instability is closely related to the types of nucleotide (GTP or GDP) that binds to the beta-tubulin. We have biochemically trapped two types of assembly states of tubulin with GTP or GDP bound representing the polymerizing and depolymerizing ends of microtubules respectively. Using cryo-electron microscopy, we have elucidated the structures of these intermediate assemblies, showing that tubulin protofilaments demonstrate various curvatures and form different types of lateral interactions depending on the nucleotide states of tubulin and the temperature. Our work indicates that during the microtubule's dynamic cycle, tubulin undergoes various assembly states. These states, different from the straight microtubule, lend the highly dynamic and complicated behavior of microtubules. Our study of microtubule's interaction with certain kinetochore complexes suggests that the intermediate assemblies are responsible for specific mechanical forces that are required during the mitosis or meiosis. Our discoveries strongly suggest that a microtubule is a molecular machine rather than a simple cellular scaffold. [Preview Abstract] |
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