Bacterial Cell Division – FtsZ mechanics, Min-FtsZ self-organization.
The discovery of cytoskeletal elements in bacteria is one of the most significant findings in cell biology over the past 20 years, but the mechanistic details remained obscure. The accurate division site selection to assemble FtsZ, a cell division protein, was suggested to be dependent on the Min proteins. However, this lacked direct experimental evidence. How FtsZ assembles into a ring-like structure was also unknown. A simple biophysical question is how do the filaments bend to assemble into a ring? To test the hypothesis that the assembly of the filaments into a ring-like structure is facilitated by intrinsic curvature of the filaments, we used modifiable curved substrates for testing the mechanical properties of FtsZ. Using this innovative approach, we showed that the FtsZ filaments possess an intrinsic curvature as well as a spontaneous twist (Arumugam et al. Angew Chem, 2012). Next, MinC is thought to couple the Min oscillations to FtsZ by direct interaction. The mechanism of inhibitory action of MinC on FtsZ assembly was not known. Using a combination of synthetic biology based reconstitution approaches, single molecule techniques and modelling, we discovered a novel mechanism where a protein uses the turnover dynamics of FtsZ to disassemble it. Using reconstitution approaches, we demonstrated an effective integrated phenomenon of self-organization and self-assembly for the first time (Arumugam et al. PNAS 2014, Bissichia et al. mBio, 2013).
Personally, this project inculcated a precept of considering stochasticity, single molecule behaviour and non-linearity in biology. With delving into self-organization behaviour by molecules and non-linearity rendered physically by molecular assemblies such as the membrane, I was drawn into the complexity of biology. I culminated the newly developed views into a review that focussed on how membranes render a very rich parameter to protein-protein interactions and give rise to complex phenomena. Further, in the article, I emphasized on how simplified systems akin to the one I utilized could be a powerful technique to understand the details of mechanisms (Arumugam et al. Wiley. Intl. Rev. Syst. Biol. Med. 2011).
(Left to Right): FtsZ filaments polymerized on a glass capilaary. FtsZ forms outward buds that are dynamic as shown by FRAP. MinD – FtsZ filaments in self-organized patterns in a MinCDE-FtsZ mix on a supported lipid bilayer.
MinCDE exploits the dynamic nature of FtsZ for its spatial regulation
S Arumugam, Zdenek Petrasek, P Schwille – PNAS, Apr 1;111(13):E1192-200. doi: 10.1073/pnas.1317764111.
MinC, MinD, and MinE Drive Counter-oscillation of Early-Cell-Division Proteins Prior to Escherichia coli Septum Formation
P Bisicchia, S Arumugam, P Schwille, D Sherratt – mBio, 2013
Surface topology engineering of membranes for the mechanical investigation of the tubulin homologue FtsZ
S Arumugam, G Chwastek, E Fischer-Friedrich,Carina Ehrig, Ingolf Mönch, Petra Schwille- Angewandte Chemie International Edition, 2012
Protein–membrane interactions: the virtue of minimal systems in systems biology
S Arumugam, G Chwastek, P Schwille – Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 2011