Cellular mechanics studied by novel nano-tools and reconstituted model systems

Abstract of PhD-thesis

In recent years biology and physics have merged to form a new emerging field called biophysics. During the last century cell research has mostly been aimed at understanding the cellular functions from a biologist point of view. However, a lot of the dynamics we observe in cells has to be explained in terms of biology, physics and even other fields like statistics and chemistry in order to achieve a complete understanding of the cell. Novel tools which have proven useful in cell research are developed by physicists like e.g. the confocal microscopy, optical tweezers and the electron microscopy to mention a few. These techniques are extremely valuable since they can visualize and manipulate in the intracellular environment at very small scales. In this thesis we explore the mechanical properties of cells using optical tweezers and confocal microscopy as our main tools. The thesis is divided in two parts whereof the first deals with mechanics of the eucaryote Schizosaccharomyces pombe (abbreviated S.pombe) whereas in the second part we want to model an intracellular property like contractility with a reconstituted system prepared from highly purified proteins. We chose to work with S.pombe due to its regular shape and due to a general simplicity of this organism. This cell is heavily used in biophysical experiments especially in relation to characterizing the mechanics of its cytoskeleton. The long term goal is to measure the polymerization forces exerted by the microtubules inside the living cell by using the optical tweezers technique. Also, we seek to measure the rheology of the S.pombe cytoplasm by using the optical trap together with inserted nano-handles. Microtubule polymerization forces and rheology of actin networks have been studied in vitro for several years whereas the mechanics of these systems in their natural in vivo environment, is poorly understood. In order to successfully measure the mechanics of S.pombe there were several technical challenges which had to be dealt with first. Most of the time was spent on finding techniques and developing procedures which could be employed in exploring the mechanics of this cell. However, several interesting projects evolved during this process some of which have been published as independent projects. In the second part the focus is more on the biophysical system. Here, we seek to model contractility with a minimal system and explore the properties and behavior of the contracting gels.

List of publications

1. Optical probing of specific and non-specific interactions with nano-meter resolution. J.K. Dreyer, P. M. Hansen, and L. B. Oddershede, Proceedings of SPIE 5514, pp. 402-409 (2004).
2. Novel optical and statistical methods reveal colloid-wall interactions inconsistent with DLVO and Lifshitz theories. P.M. Hansen, J. K. Dreyer, J. F.-Borg, and L. Oddershede, J Colloid Interface Sci. 2005 Jul 15;287(2):561-71.
3. Tweezercalib 2.0: Faster version of Matlab package for precise calibration of optical tweezers. Hansen, P.M.; Tolic´-Nørrelykke, I.M,; Flyvbjerg, H.; Berg-Sørensen K. Comput. Phys. Commun. DOI information: 10.1016/j.cpc.2005.11.007.
4. Expanding the optical trapping range of gold nanoparticles. Hansen, P.M.;Bhatia, V.K.;Harrit, N.;Oddershede, L. Nano Lett., 5 (10), 1937 -1942, 2005
5. Optical trapping inside living organisms. P. M. Hansen, L. Oddershede, SPIE proceedings 5930 (2005).
6. Vild med lys. P.M. Hansen, T. W. Madsen & L. Oddershede. Artikel i KVANT, nr. 4 december 2005.
7. Tweezercalib 2.1: Faster version of MatLab package for precise calibration of optical tweezers. Hansen, P.M.; Tolic´-Nørrelykke, I.M,; Flyvbjerg, H.; Berg-Sørensen K. Comput. Phys. Commun. vol 175, pp. 572-573 (2006)
8. Finite time singularity assists cell division Z. Lansky, P.M. Hansen, and L. Oddershede, preprint.
9. Contractile behavior of crosslinked actin-myosin networks. P.M. Hansen, G. Koenderink, Z. Dogic, B. Brieher, D. Cuvelier, L. Mahadevan, and D.A. Weitz. Preprint (will be submitted to PNAS).
10. Active stiffening of biopolymer networks driven by molecular motors. G.H. Koenderink, Z. Dogic, F. Nakamura, P.M. Hansen, J.H. Hartwig, T.P. Stossel, D.A. Weitz (submitted)

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