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Alumni Ebbinghaus publishes new research on Macromolecular crowding effect

1/22/2015

 

A central dogma in crowding theories was that crowding effects are solely mediated by hard-core repulsions between the macromolecules and therefore steric excluded volume effects. This ideal excluded volume effect would result in an entropic stabilization of a protein while the enthalpy remains unchanged. However, using artificial crowding agents like Ficoll 70 former CPLC fellow Simon Ebbinghaus and his students Michael Senske and David Gnutt have recently shown that crowding effects on protein stability can be primarily mediated by enthalpic effects (1). In the cellular environment, excluded volume effects are further compensated by unspecific interactions (2). However, hypertonic stress can evoke significant excluded volume effects that lead to high compression forces acting on biomolecules in cells (2). Such effects could endanger proteostasis and promote protein aggregation.

Simon Ebbinghaus has been a Assistent Professor at the Ruhr-University Bochum (Department of Physical Chemistry II) since 2011. Before that, he worked as a Feodor Lynen and CPLC Fellow with Martin Gruebele at the University of Illinois (Urbana-Champaign) from 2008 to 2010. For more details, see www.rub.de/pc2/ebbinghaus.

 

 

(1) M. Senske, L. To¨rk, B. Born, M. Havenith, C. Herrmann, S. Ebbinghaus. Protein Stabilization by Macromolecular Crowding through Enthalpy rather than Entropy. J. Am. Chem. Soc., 136(25): 9036–9041, 2014.

(2) D. Gnutt, M. Gao, O. Brylski, M. Heyden and S. Ebbinghaus. Excluded volume effects in the living cell. Angew. Chem. Int. Ed., Accepted Manuscript, DOI: 10.1002/anie.201409847R1

1/10/2014 Michael Assaf, Elijah Roberts, Zaida Luthey-Schulten, and Nigel Goldenfeld,

Extrinsic noise
Extrinsic noise
In a new collaborative direction between Luthey-Schulten and Goldenfeld, the work is primarily analytical, and will help us understand the emergence of heterogeneous cell populations in initially clonal bacterial populations. Biological systems are of great interest to statistical physicists, because they contain a large number of strongly fluctuating degrees of freedom, but not enough that they are in the thermodynamic limit.  Accordingly the noise characteristics and the dynamical behavior of such systems pose a unique challenge to theory that is rarely encountered in other areas of physics, leading to important biological phenomena.  A population of clonal cells can become phenotypically differentiated as a result of environmental (i.e. extrinsic) noise and intrinsic noise, such as number fluctuations. These phenomena are now well understood in the case where intrinsic gene expression stochasticity is the key noise source.  But what is the role of extrinsic noise, arising from cell-to-cell variations in (e.g.) ribosome or RNA polymerase number, thus equally affecting each gene within the cell?  How do mean switching times between allowed states depend on the extrinsic noise?

To address this, Goldenfeld and Luthey-Schulten have solved the problem of phenotype switching due to a single self-regulating gene with positive feedback.  The technical advance that they and their CPLC associated postdocs introduced in this context was to use WKB and Hamilton-Jacobi methods to go beyond simple mass-action results.  The key result was that the different phenotypes' lifetime is significantly altered, with increased parameter range for bistability.  The mean switching time is lowered by many orders of magnitude even for a very moderate amount of extrinsic noise, which is important for bacterial communities that exploit heterogeneity in order to inhabit new ecological niches, for example.  The semi-analytical results were validated through state of the art stochastic simulations available through the Luthey-Schulten’s Lattice Microbe software (E. Roberts et al. JCC (2013)).

The intire article can be viewed at Phys. Rev. Lett., 2013, Volume  111, Pages 058102.