(757e) Membrane Remodelling By Proteins and Nanostructure

Membrane remodelling plays a critical role in many physical and biological/cellular processes including synthetic biology, drug delivery, cellular uptake of nano containers, and self-assembly of nanostructures at membrane interface. The atomistic membrane simulations are however extremely slow to simulate membrane behaviour at large time and length scales. We have developed a triangulated coarse-grained membrane model which is capable of rapid and efficient simulation of membrane remodelling. We performed Monte Carlo simulations of the model to investigate membrane interaction with nanoparticles and proteins. We report tubular membrane structures induced by adsorbed nanoparticles on vesicles [1] and investigate the role of membrane curvature [2,3] and size and shape of the particles [4] on cellular uptake of the particles. We also show how membrane curvature determines pairwise interactions induced between adsorbed Janus nanoparticles on the vesicles [5] and reveal that the area fraction of the adhesive Janus particle surface is an important control parameter for the assembly of the particles [5].

We also performed simulations to understand how tubular membrane structures of the Endoplasmic reticulum , Golgi, mitochondria, and other cellular organelles are created and maintained. Our simulations show that the membrane area growth and volume reduction can induce tubular membrane structure in concert with curved proteins previously found to shape these tubules [6].

We use our model to simulate membrane remodelling induced by protein molecules in biological processes. Our simulations reveal the scaffolding role of Atg protein complexes in autophagosome biogenesis in autophagy, a critical physiological process winning the Nobel prize of medicine in 2016. We show that cooperative interaction of aggregates of several protein chains is essential to remodel the membrane appropriately [7]. Our outstanding results, in collaboration with experimental colleagues from Berkeley, indicate how ESCRT (endosomal sorting complex required for transport) machinery can induce membrane remodelling and scission [8].

References

(1) Bahrami, A. H., Lipowsky, R., & Weikl, T. R., Phys. Rev. Lett. 2012, 109, 188102.

(2) Bahrami, A. H. et. al, Advances in colloid and interface science 2014, 208, 214-224.

(3) Bahrami, A. H., Lipowsky, R., & Weikl, T. R., Soft Matter 2016, 12(2), 581-587.

(4) Bahrami, A. H., Soft Matter 2013, 9(36), 8642-8646.

(5) Bahrami, A. H., & Weikl, Nano Letters 2018, 18(2), 1259-1263.

(6) Bahrami, A. H., & Hummer, G., ACS Nano 2017, 11(9), 9558-9565.

(7) Bahrami, A. H., Lin, M. G., Ren, X., Hurley, J. H., & Hummer, G., PLOS Comput. Biol. 2017, 13(10).

(8) Schoeneberg, J. et. al, Science 362 (6421), 1423-1428.