The plasma-membrane of the cell are highly heterogeneous in their lateral organization and their interactions with embedded and peripheral proteins. This heterogeneity is an important parameter in providing mechanisms by which various biological processes are regulated. The cell-membrane is highly complex and dynamic and required capturing processes in real time to be able to understand them. In the past, using giant unilamellar vesicles formed from a quaternary lipid mixture, we have demonstrated experimentally the effect of a cytoskeletal pinning on phase separation and coexistence in freestanding multicomponent lipid membranes.
Movie. FtsZ filaments assembling on a phase-separated vesicle consisting of four lipid components (Arumugam et al. Biophys J. 2015)
We also investigated the hypothesis that the thermal fluctuations of the membrane could drive membrane associated proteins or nano-particles to cluster together, in a similar manner to Casimir forces. Experimental verification of this hypothesis needed a sophisticated approach involving an amalgamation of micropipette aspiration and fluorescence correlation spectroscopy (FCS). By combining these experimental approaches with simulations, we showed that membrane fluctuations could drive clustering of proteins and provided a first-time demonstration of the concept of Casimir-like forces biological systems (Pezeshkian*, Gao*, Arumugam* et al. ACS Nano, 2017).
We are further interested in understanding how membrane protrusions are regulated by actin and associated proteins as well as understanding how membrane associated proteins move on the membrane driven by acto-myosin forces. We have now combined optogenetic manipulations with Lattice Light-Sheet Microscopy.
Mechanism of Shiga Toxin Clustering on Membranes
Weria Pezeshkian°, Haifei Gao°, Senthil Arumugam°, Ulrike Becken, Patricia Bassereau, Jean-Claude Florent, John Hjort Ipsen, Ludger Johannes, and Julian C. Shillcock. ° equal first authors.
ACS Nano, 10.1021/acsnano.6b05706 (2016)
Cytoskeletal pinning controls phase separation in multicomponent lipid membranes
Senthil Arumugam, Eugene P Petrov and Petra Schwille.
Biophysical Journal. (2015).
Membrane nanodomains: contribution of curvature and interaction with proteins and cytoskeleton
Senthil Arumugam and Patricia Bassereau
Essays Biochem. (2015) 57, 1–11: doi: 10.1042/BSE0570001