Interaction of α‐Synuclein with Phospholipids and the Associated Restructuring of Interfacial Lipid Water: An Interface‐Selective Vibrational Spectroscopic Study

Abstract

Interaction of α‐Synuclein (αS) with biological lipids is crucial for the onset of its fibrillation at the cell membrane/water interface. Probed herein is the interaction of αS with membrane‐mimicking lipid monolayer/water interfaces. The results depict that αS interacts negligibly with zwitterionic lipids, but strongly affects the pristine air/water and charged lipid/water interfaces by perturbing the structure and orientation of the interfacial water. The net negative αS (−9 in bulk water; pH 7.4) reorients the water as hydrogen‐up (H‐up) at the air/water interface, and electrostatically interacts with positively charged lipids, making the interface nearly net neutral. αS also interacts with negatively charged lipids: the net H‐up orientation of the interfacial water decreases at the anionic lipid/water interface, revealing a domain‐specific interaction of net negative αS with the negatively charged lipids at the membrane surface.

Effects of stearyl alcohol monolayer on the structure, dynamics and vibrational sum frequency generation spectroscopy of interfacial water

“…In addition to pure water-air interfaces, the VSFG spectroscopy of the OH stretch modes of water has also been used for studies of aqueous interfaces with a variety of complex solutes. [17][18][19][20][34][35][36][37][38][39][40] Apart from the OH stretch modes of water, there have also been studies where the VSFG spectrum in the C-H stretching region has also been connected to the order/disordered monolayer and orientation of alkyl groups of alcohols, lipids and other organic substances at aqueous surfaces. [40][41][42][43] In a recent work, 44 we investigated the interfacial behavior of water covered by a layer of tertiary butyl alcohol (TBA) which carries a fully branched hydrophobic part.…”

DNA-Induced Restructuring of Interfacial Water and the Hydrocarbon Chain of Different Forms of Fungicide at the Water Interface: Vibrational Sum Frequency Generation Study

“…29−34 Indeed, VSFG has also been able to decode the properties of several complex biological interfaces, such as flip-flop of water molecules at the lipid/water interfaces, 35,36 conformation changes of proteins at membrane interfaces, 21,22 effect of cholesterol on the ordering of the hydrocarbon chain of lipids, 37 and role of water in the aggregation of disordered proteins. 26,38 Apart from the soft interfaces, VSFG has also been utilized to extract the interfacial properties of minerals, metals, as well as electrode interfaces. 39−41 These studies demonstrated the capability of the VSFG technique to decode the complex behavior of different interfaces.…”

Restructuring of Membrane Water and Phospholipids in Direct Interaction of Neurotransmitters with Model Membranes Associated with Synaptic Signaling: Interface-Selective Vibrational Sum Frequency Generation Study

“…Neurotransmitters have complex interactions with phospholipids as well as interfacial membrane water which may affect its functionality . Indeed, it has been already known that the interfacial water beneath the phospholipid plays a key role in the stability of the membrane as well as fibrillation and conformation change of different proteins at the membrane. − Hence, understanding the structure of phospholipid and its associated interfacial water during the direct interaction of neurotransmitters with the membrane is essential to get insight into the synaptic signaling process. However, earlier experimental studies of neurotransmitter binding with lipid could not provide insight into the property and structure of the synaptic membrane region because of the lack of interface selectivity of the techniques. ,, …”

“…Vibrational sum frequency generation (VSFG) is an interface-specific and sensitive technique that has been utilized extensively to decode the properties of several different complex interfaces. − The VSFG technique has been applied to understand the structure of surface water at the surfactant/water, lipid/water, and protein/lipid/water interfaces. − Apart from that, the conformational changes of proteins, as well as structural changes of lipid at different soft interfaces, has also been investigated using the VSFG technique. ,,, Indeed, recently, our group has utilized the VSFG technique to show that the adsorption of monomeric α-synuclein reorganizes membrane water depending on the headgroup of the lipid, which affects the fibrillation process of protein as well …”

“…24,33,34,36 Indeed, recently, our group has utilized the VSFG technique to show that the adsorption of monomeric α-synuclein reorganizes membrane water depending on the headgroup of the lipid, which affects the fibrillation process of protein as well. 22 In order to get insight into the structure of phospholipid and associated surface water during the direct interaction of neurotransmitters with the membrane, the VSFG spectra of the anionic (1,2-dipalmitoyl-sn-glycero-3-phospho-rac-1-glycerol sodium salt (DPPG)) and zwitterionic (1,2-dipalmitoylsn-glycero-3-phosphocholine (DPPC)) phospholipid monolayer/water interfaces in the absence and presence of dopamine, as well as serotonin neurotransmitters in the aqueous phase, have been measured (structures of all the chemicals are provided in Figure 1). Zwitterionic and anionic phospholipids are chosen as model membrane systems as they are the significant contributors of the neuronal synaptic membranes.…”