A Water Window on Membrane Biochemistry & Physics: From Water to Neurons

Abstract: Lipid cell membranes are essential for life: They are a dynamic compartmentalized environment, a localized space for proteins to perform their functions, and select what enters the cell. Although recognized as an essential building block, water is usually treated as a background for biology. However, water is a crucial mediator of chemical change and determines the structure of the membrane. The study of lipid membranes is generally pursued by following either a top-down approach, introducing labels to living cell membranes or a bottom-up approach with well-controlled but over-simplified membrane monolayer or supported membrane models. In the first approach molecular level hydration information is lost, while in the second approach the connection with real bilayer membranes is limited. 

Recent work in our laboratory offers an alternative path that ultimately envisions bringing together both top-down and bottom-up approaches. By using intermediate nano-, micro- and macroscale free-floating membrane systems in combination with novel nonlinear optical spectroscopy and imaging methods, we advance the understanding of realistic membranes on a more fundamental level, yet allowing for the complexity of living systems [1]. In this presentation I will first introduce high throughput wide-field second harmonic imaging, which enables the label-free imaging of interfacial (< 1 nm thick) water [2], with a spatial resolution of ~370 nm and using  ~100 ms acquisition times per image. We obtain information about the orientational order of water and use this interfacial response to create spatiotemporal membrane potential maps of free standing lipid membranes in solution [3]. These maps are then used to quantify divalent – membrane interactions, which show surprisingly heterogeneous behavior that deviates from predictions by mean field. Finally, I will show how water in operating ion channels can be SH imaged and understood [4], and how this can be used to directly visualize neuronal activity in brain cells [5]. 

References

[1] - Chemistry of Lipid Membranes from Models to Living Systems: A Perspective of Hydration, Surface Potential, Curvature, Confinement and Heterogeneity, Halil I. Okur, Orly B. Tarun, S. Roke, J. Am. Chem. Soc., (2019), 141, 31, 12168.

[2] - Optical Imaging of Surface Chemistry and Dynamics in Confinement, C. Macias-Romero, I. Nahalka, H. I. Okur, S. Roke, Science (2017) 357, 784.

[3] - A label-free and charge-sensitive dynamic imaging of lipid membrane hydration on millisecond time scales, O. Tarun, C. Hannesschläger, P. Pohl, and S. Roke, Proc. Nat. Acad. Sci. USA (2018) 115, 4081.

[4] - Transient domains of ordered water induced by divalent ions lead to lipid membrane curvature fluctuations, O.B. Tarun, H.I. Okur, P. Rangamani, S. Roke, Commun. Chem. (2020) 3 (1), 1-8.

[5] - Spatiotemporal Imaging of Water in Operating Voltage-Gated ion Channels Reveals the Slow Motion of Interfacial Ions, O. B. Tarun, M. Y. Eremchev, A. Radenovic, and S. Roke, Nano Lett. (2019), 19, 7608.

[6] - Membrane water for probing neuronal membrane potentials and ionic fluxes at the single cell level, M. Didier, O. Tarun, P. Jourdain, P. Magistretti, S. Roke, Nat. Commun. (2018), 9, 5287