Hydration Dynamics in Biological Membranes: Emerging Applications of Terahertz Spectroscopy

Abstract

Water drives the spontaneous self-assembly of lipids and proteins into quasi two-dimensional biological membranes that act as catalytic scaffolds for numerous processes central to life. However, the functional relevance of hydration in membrane biology is only beginning to be addressed, predominantly because of challenges associated with direct measurements of hydration microstructure and dynamics in a biological milieu. Our recent work on the novel interplay of membrane electrostatics and crowding in shaping membrane hydration dynamics utilizing terahertz (THz) spectroscopy represents an important step in this context. In this Perspective, we provide a glimpse into the ever-broadening functional landscape of hydration dynamics in biological membranes in the backdrop of the unique physical chemistry of water molecules. We further highlight the immense (and largely untapped) potential of the THz toolbox in addressing contemporary problems in membrane biology, while emphasizing the adaptability of the analytical framework reported recently by us to such studies.

Terahertz Spectroscopic Analysis in Protein Dynamics: Current Status

“…In fact, membrane proteins are those that in this context are most involved in the interaction with water, with possible changes in the structure and the ability to create a network of hydrogen bonds, which can be explored from 1 to 6 THz. Pal and Chattopadhyay [204] probably provided the first and accurate overview of the potential of THz spectroscopy in this area. They demonstrated how THz-TDS and some optical parameters (e.g., the dielectric constant) can describe specific changes in the membrane microenvironment and lipid concentration.…”

Site-directed fluorescence approaches to monitor the structural dynamics of proteins using intrinsic Trp and labeled with extrinsic fluorophores

“…The presence or absence of REES can therefore distinguish between the restricted/bound and bulk/free water molecules around the fluorophore’s microenvironment. Since hydration dynamics plays a key role in membrane dynamics and in fine tuning the functionality of proteins in a variety of ways ( Raghuraman et al., 2014 ; Bellisent-Funel et al., 2016 ; Ball, 2017 ; Pal and Chattopadhyay, 2021 ), REES has been utilized to monitor the folding and aggregation of proteins, lipid-protein interactions, membrane dynamics and heterogeneity, function-dependent hydration dynamics, discrete protein conformational states etc. Please refer to recent review ( Brahma and Raghuraman, 2021 ) for REES and its applications.…”

Addition of cholesterol alters the hydration at the surface of model lipids: a spectroscopic investigation

“…[26][27][28][29][30] It can directly probe the permanent and induced dipole moments of water molecules present at the interface of biomolecules such as proteins 31,32 and lipids. 21,22,33 The total dipole moment is directly correlated with the absorption coefficient of the systems; thus, any change in the absorption coefficient of a solution manifests an alteration in the hydration behaviour of the solute molecules. [34][35][36] Measurements of the frequency dependent absorption coefficient therefore offers an effective avenue to directly probe lipid hydration.…”