Leif Matsson

Associate professor

Contact address
Department of Physics
University of Gothenburg
SE-412 96 Göteborg, Sweden - Tel: 46 31772 1000; 46 709400594.
leif.matsson@telia.com; leif.matsson@physics.gu.se

Homepages
http://www.biomedicine.gu.se/leifmatsson
http://www.chalmers.se/ap/EN/research/condensed-matter-theory

Current field of interest
The main focus in my research is to understand cell cycle dynamics from a condensed matter and molecular physics point of view, such as in DNA replication [1-5, 7, 8] and segregation [11]. I am also interested in ion-channels [6, 9] and motor proteins [10].

Research topics include
1. DNA replication.
2. Spindle checkpoint and segregation.
3. Relationship between native DNA dynamics and
single DNA molecule force-extension formula.
4. Non-equilibrium statistical mechanics.
5. Motor proteins.
6. Ion channels.

Spindle checkpoint problem
The spindle checkpoint, which blocks segregation of replicated chromosomes until all sister chromatid (SC) pairs have been stably connected to the two spindle poles (bi-oriented), has been classed as perhaps the biggest mystery of the cell cycle. In the spindle checkpoint machinery the molecular physics and condensed matter properties of the spindle-SC system come to clear expression. The spatial correlations between bi-oriented SC pairs then become directly observable at the metaphase plate (Fig. 1). Moreover, to reach the threshold for metaphase-anaphase transition, the number of bi-oriented SCs pairs must increase. Non-equilibrium conditions combined with this type of spatial correlations create a problem beyond current physical knowledge. Thus the spindle checkpoint problem has been confined in a gap between molecular biology and condensed matter physics, like a modern quinta essentia type problem. By the use of a non-equilibrium probability theory, a solution to this problem was recently obtained in the form of a non-equilibrium collective spindle-SC interaction (see under “condensed matter” at http://Select.iop.org), which seems to possess the most essential spindle checkpoint functions such as blocking and synchronization of segregation and a good estimate of the frequency of kinetochore oscillations [11]. The almost constant amplitude of the observed kinetochore oscillations in anaphase is interpreted such that dissipative forces in this dynamical system are approximately compensated by the effect on these oscillations of the progressive proteolytic cleavage of cohesion molecules.

Figure text

Non-equilibrium statistical mechanics
The current understanding of non-equilibrium statistical mechanics is limited to non-rigid condensed matter systems. However, as explained above, the spindle checkpoint machinery works at non-equilibrium chemical conditions and contains spatial correlations. A solution to this problem was obtained by the use of a non-equilibrium statistical mechanics [11], and it was shown that the order parameter in such a non-equilibrium system corresponds to the grand partition function in equilibrium statistical mechanics. However, contrary to equilibrium systems, in which the number of particles is only allowed to fluctuate, in the spindle-SC system the order parameter is linked directly to the non-equilibrium reaction, implying that the number of particles (stably attached kinetochore complexes) increases.

It is sometimes claimed that there is no difference between equilibrium dynamics and non-equilibrium dynamics in the slow interaction limit. However, the obtained spindle checkpoint dynamics [11] shows that this is not the case. Depending on how the slow interaction limit is approached one obtain different results, which is illustrated by the following example. In equilibrium systems the order parameter is usually temperature dependent (thermotropic system), but in the actual non-equilibrium system the order parameter depends on the density of constituent particles (lyotropic system). This is of crucial importance here because the lyotropic order parameter also provides a coarse-grained mapping between the (microscopic) molecular level and the macroscopic level, at which decisions such as to segregate or not to segregate are made.

Figure text

Relationship to single DNA molecule studies
Stretching a single-DNA molecule by an external force is not what happens in living cells. Nevertheless, during the spindle assembly process something similar happens. The attaching microtubules then exert opposite pulling forces on the two sister kinetochores, generating tension in centromeric chromatin (Fig. 2). As demonstrated in the work on spindle checkpoint problem [11], despite that chromatin is expected to be more complex than DNA, tension in this native spindle-SC system can be related to the force-extension formula observed in the laboratory. Hopefully this relationship can be used to translate results from single molecule force spectroscopy studies to living cell conditions.

Publications in Biological physics

1. L. Matsson, Soliton growth-signal transduction in topologically   quantized T cells. Phys. Rev. E 48, 2217-2231 (1993).
2. L. Matsson, Response theory for nonstationary ligand-receptor interaction and a solution to the growth signal firing problem. J. Theor. Biol. 180, 93-104 (1996).
3. L. Matsson, Long range interaction between protein complexes in DNA controls replication and cell cycle progression. J. Biol. Syst. 9 (No. 1), 41-65 (2001).
4. L. Matsson, DNA replication and cell cycle progression regulated by long range interaction between protein complexes bound to DNA. J. Biol. Phys. 27, 329-359 (2001).
5. L. Matsson, Long range force between pre-replication complexes Pre-RC) in DNA controls replication and cell cycle progression. J. Biol. Phys. 28, 675-701 (2002).
6. L. Matsson, Virulh Sa-yakanit, and Santipong Boribarn, Ligand gated ion channel currents in nonstationary lyotropic model, Neurochemical Research 28, 377-384 (2003).
7. L. Matsson, and Adrian Parsegian, Completing our first decade of biological physics conferences. J. Biol. Phys. 31, 235-239 (2005).
8. L. Matsson, Model of DNA dynamics and replication. J. Biol. Phys. 31, 303-321 (2005).
9. L. Matsson, Virulh Sa-yakanit, and Santipong Boribarn, Lyotropic ion channel current model compared with Ising model. J. Biol. Phys. 31, 525-532 (2005).
10. Miljko V. Sataric, Leif Matsson and Jack A. Tuszynski, Complex movements of motor protein relay helices during the power stroke. Phys. Rev. E 74, 051902 (2006).
11. L. Matsson, Spindle checkpoint regulated by non-equilibrium collective spindle-chromosome interaction; Relationship to single DNA molecule force-extension formula. J. Phys. Cond. Matter 21, 502101 (2009) http://select.iop.org.

Conference proceedings

1. “Nonlinear cooperative phenomena in biological systems”. Editor Leif Matsson, World Scientific, Singapore 1998. The conference was held 19-22 August 1977 at ICTP, Trieste.

2. “The first workshop on biological physics 2000”. Editors: Virulh Sayakanit, Leif Matsson and Hans Frauenfelder, World Scientific, Singapore 2001. The conference was held 18-22 September 2000 at Chulalongkorn University, Bangkok.

3. “The 5th international conference on biological physics”. J. Biol. Phys. (3/4) 31 (2005). Guest editor Leif Matsson. The conference was held 23-27 August 2004 at Gothenburg University and Chalmers University of Technology, Gothenburg.

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Appendix A2
Appendix A3